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Pets and Immunomodulation

  • Luis Taborda-BarataEmail author
Chapter

Abstract

The immune system is fundamental for survival. Its development and functions are modulated by various genetic and environmental factors. Pets are an important environmental factor, and pet ownership may have relevant immunomodulatory effects. Pets may induce immune modulation via changes induced in gut, cutaneous and respiratory microbiome in pet owners. Such immunomodulation-associated changes may have positive health outcomes. In fact, these may include a contribution towards reducing the risk of developing allergic diseases, if exposure to pets begins in early infancy. In addition, pet ownership may also have other beneficial health effects, namely, reduced psychological stress and depression, which, in turn, may be associated with positive immunomodulatory effects. Finally, pets may also stimulate their owners to have higher levels of regular physical activity and exercise, activities that also have potentially positive effects upon various functions of their owners’ immune system.

Keywords

Pets Pet owners Immune system Immune modulation Microbiome Allergies Stress Depression Physical activity 

Notes

Acknowledgements

I would like to thank Professor Maria Vaz Patto, MD, PhD, for her kind patience and helpful assistance.

References

  1. Abraham C, Cho JH (2009) Inflammatory bowel disease. N Engl J Med 361:2066–2078.  https://doi.org/10.1056/NEJMra0804647CrossRefGoogle Scholar
  2. Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC (2012) Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 129:434–440.  https://doi.org/10.1016/j.jaci.2011.10.025CrossRefGoogle Scholar
  3. Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC (2014) Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy 44:842–850.  https://doi.org/10.1111/cea.12253CrossRefGoogle Scholar
  4. Aichbhaumik N, Zoratti EM, Strickler R, Wegienka G, Ownby DR, Havstad S et al (2008) Prenatal exposure to household pets influences fetal immunoglobulin E production. Clin Exp Allergy 38:1787–1794.  https://doi.org/10.1111/j.1365-2222.2008.03079.xCrossRefGoogle Scholar
  5. Anderson WP, Reid CM, Jennings GL (1992) Pet ownership and risk factors for cardiovascular disease. Med J Aust 157:298–301CrossRefGoogle Scholar
  6. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341.  https://doi.org/10.1126/science.1198469CrossRefGoogle Scholar
  7. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Sears MR et al (2013) Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity. Allergy Asthma Clin Immunol 9:15.  https://doi.org/10.1186/1710-1492-9-15CrossRefGoogle Scholar
  8. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL (2000) Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med 343:538–543CrossRefGoogle Scholar
  9. Baptista AP, Olivier BJ, Goverse G, Greuter M, Knippenberg M, Kusser K et al (2013) Colonic patch and colonic SILT development are independente and differentially regulated events. Mucosal Immunol 6:511–521.  https://doi.org/10.1038/mi.2012.90CrossRefGoogle Scholar
  10. Barberán A, Dunn RR, Reich BJ, Pacifici K, Laber EB, Menninger HL et al (2015) The ecology of microscopic life in household dust. Proc Biol Sci 282(1814).  https://doi.org/10.1098/rspb.2015.1139CrossRefGoogle Scholar
  11. Barker SB, Pandurangi AK, Best AM (2003) Effects of animal-assisted therapy on patients’ anxiety, fear, and depression before ECT. J ECT 19:38–44CrossRefGoogle Scholar
  12. Barker SB, Knisely JS, McCain NL, Best AM (2005) Measuring stress and immune responses in healthcare professionals following interaction with a therapy dog: a pilot study. Psychol Rep 96:713–729CrossRefGoogle Scholar
  13. Bauer H, Horowitz RE, Levenson SM, Popper H (1963) The response of the lymphatic tissue to microbial flora. Studies on germfree mice. Am J Pathol 42:471–483Google Scholar
  14. Bauman AE, Russell SJ, Furber SE, Dobson AJ (2001) The epidemiology of dog walking: an unmet need for human and canine health. Med J Aust 175:632–634CrossRefGoogle Scholar
  15. Beetz A, Kotrschal K, Hediger K, Turner D, Uvnäs-Moberg K (2011) The effect of a real dog, toy dog and friendly person on insecurely attached children during a stressful task: an exploratory study. Anthrozoös 24:349–368CrossRefGoogle Scholar
  16. Beetz A, Uvnäs-Moberg K, Julius H, Kotrschal K (2012) Psychosocial and psychophysiological effects of human-animal interactions: the possible role of oxytocin. Front Psychol 3:234.  https://doi.org/10.3389/fpsyg.2012.00234CrossRefGoogle Scholar
  17. Berget B, Braastad BO (2011) Animal-assisted therapy with farm animals for persons with psychiatric disorders. Ann Ist Super Sanita 47:384–390.  https://doi.org/10.4415/ANN_11_04_10CrossRefGoogle Scholar
  18. Bergroth E, Remes S, Pekkanen J, Kauppila T, Büchele G, Keski-Nisula L (2012) Respiratory tract illness during the first year of life: effect of dog and cat contacts. Pediatrics 130:211–220.  https://doi.org/10.1542/peds.2011-2825CrossRefGoogle Scholar
  19. Bermon S, Petriz B, Kajeniene A, Prestes J, Castell L, Franco OL (2015) The microbiota: an exercise immunology perspective. Exerc Immunol Rev 21:70–79Google Scholar
  20. Bigley AB, Simpson RJ (2015) NK cells and exercise: implications for cancer immunotherapy and survivorship. Discov Med 19:433–445Google Scholar
  21. Billingham RE, Brent L, Medawar PB (1956) Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance. Trans R Soc Lond B Biol Sci 239:357–414CrossRefGoogle Scholar
  22. Bisgaard H, Li N, Bonnelykke K, Chawes BL, Skov T, Paludan-Müller G et al (2011) Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 128:646–652.  https://doi.org/10.1016/j.jaci.2011.04.060CrossRefGoogle Scholar
  23. Bjerg A, Ekerljung L, Eriksson J, Naslund J, Sjolander S, Ronmark E et al (2016) Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood. Clin Exp Allergy 46:1328–1336.  https://doi.org/10.1111/cea.12757CrossRefGoogle Scholar
  24. Bjorksten B, Sepp E, Julge K, Voor T, Mikelsaar M (2001) Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 108:516–520CrossRefGoogle Scholar
  25. Blair SN, Kohl HW III, Barlow CE, Paffenbarger RS Jr, Gibbons LW, Macera CA (1995) Changes in physical fitness and all-cause mortality: a prospective study of healthy and unhealthy men. JAMA 273:1093–1098CrossRefGoogle Scholar
  26. Blum JS, Wearsch PA, Cresswell P (2013) Pathways of antigen processing. Annu Rev Immunol 31:443–473.  https://doi.org/10.1146/annurev-immunol-032712-095910CrossRefGoogle Scholar
  27. Bufford JD, Reardon CL, Li Z, Roberg KA, DaSilva D, Eggleston PA et al (2008) Effects of dog ownership in early childhood on immune development and atopic diseases. Clin Exp Allergy 38:1635–1643.  https://doi.org/10.1111/j.1365-2222.2008.03018.xCrossRefGoogle Scholar
  28. Burnet FM (1940) Biological aspects of infectious diseases. Macmillan; New YorkGoogle Scholar
  29. Burr ML, Merrett TG, Dunstan FD, Maguire MJ (1997) The development of allergy in high-risk children. Clin Exp Allergy 27:1247–1253CrossRefGoogle Scholar
  30. Bustos-Mrán E, Blas-Rus N, Martín-Cófreces NB, Sánchez-Madrid F (2016) Orchestrating lymphocyte polarity in cognate imune cell-cell interactions. Int Rev Cell Mol Biol 327:195–261.  https://doi.org/10.1016/bs.ircmb.2016.06.004CrossRefGoogle Scholar
  31. Cahenzli J, Köller Y, Wyss M, Geuking MB, McCoy KD (2013) Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe 14:559–570.  https://doi.org/10.1016/j.chom.2013.10.004CrossRefGoogle Scholar
  32. Casas L, Tischer C, Wouters IM, Torrent M, Gehring U, García-Estebán R et al (2013) Early life microbial exposure and fractional exhaled nitric oxide in school-aged children: a prospective birth cohort study. Environ Health 12:103.  https://doi.org/10.1186/1476-069X-12-103CrossRefGoogle Scholar
  33. Chaplin DD (2010) Overview of the immune response. J Allergy Clin Immunol 125:S3–S23.  https://doi.org/10.1016/j.jaci.2009.12.980CrossRefGoogle Scholar
  34. Charnetski CJ, Riggers S, Brennan FX (2004) Effect of petting a dog on immune system function. Psychol Rep 95:1087–1091CrossRefGoogle Scholar
  35. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S et al (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488:178–184.  https://doi.org/10.1038/nature11319CrossRefGoogle Scholar
  36. Clarke SF, Murphy EF, O’Sullivan O, Lucey AJ, Humphreys M, Hogan A et al (2014) Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63:1913–1920.  https://doi.org/10.1136/gutjnl-2013-306541CrossRefGoogle Scholar
  37. Cohen S (2005) Keynote presentation at the eight international congress of behavioral medicine: the Pittsburgh common cold studies: psychosocial predictors of susceptibility to respiratory infectious illness. Int J Behav Med 12:123–131CrossRefGoogle Scholar
  38. Cole KM, Gawlinski A, Steers N, Kotlerman J (2007) Animal-assisted therapy in patients hospitalized with heart failure. Am J Crit Care. 16:575–585Google Scholar
  39. Cresci GA, Bawden E (2015) Gut microbiome: what we do and don’t know. Nutr Clin Pract 30:734–746.  https://doi.org/10.1177/0884533615609899CrossRefGoogle Scholar
  40. Cutt H, Giles-Corti B, Knuiman M, Timperio A, Bull F (2008) Understanding dog owners’ increased levels of physical activity: results from RESIDE. Am J Public Health 98:66–69CrossRefGoogle Scholar
  41. Dannemiller KC, Gent JF, Leaderer BP, Peccia J (2016) Influence of housing characteristics on bacterial and fungal communities in homes of asthmatic children. Indoor Air 26:179–192.  https://doi.org/10.1111/ina.12205CrossRefGoogle Scholar
  42. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S et al (2010) Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci 107:14691–14696.  https://doi.org/10.1073/pnas.1005963107CrossRefGoogle Scholar
  43. Dembicki D, Anderson J (1996) Pet ownership may be a factor in improved health of the elderly. J Nutr Elder 15:15–31CrossRefGoogle Scholar
  44. den Haan JM, Arens R, van Zelm MC (2014) The activation of the adaptive immune system: cross-talk between antigen-presenting cells, T cells and B cells. Immunol Lett 162(2 Pt B):103–112.  https://doi.org/10.1016/j.imlet.2014.10.011CrossRefGoogle Scholar
  45. Dhabhar FS, Malarkey WB, Neri E, McEwen BS (2012) Stress-induced redistribution of immune cells - from barracks to boulevards to battlefields: a tale of three hormones –Curt Richter Award Winner. Psychoneuroendocrinology 37:1345–1368.  https://doi.org/10.1016/j.psyneuen.2012.05.008CrossRefGoogle Scholar
  46. Dicksved J, Floistrup H, Bergstrom A, Rosenquist M, Pershagen G, Scheynius A et al (2007) Molecular fingerprinting of the fecal microbiota of children raised according to different lifestyles. Appl Environ Microbiol 73:2284–2289CrossRefGoogle Scholar
  47. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci 107:11971–11975.  https://doi.org/10.1073/pnas.1002601107CrossRefGoogle Scholar
  48. Dominguez-Gerpe L, Rey-Mendéz M (2001) Alterations induced by chronic stress in lymphocyte subsets of blood and primary and secondary immune organs of mice. BMC Immunol 2:7.  https://doi.org/10.1186/1471-2172-2-7CrossRefGoogle Scholar
  49. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK et al (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457.  https://doi.org/10.1016/j.biopsych.2009.09.033CrossRefGoogle Scholar
  50. Duggal NA, Upton J, Phillips AC, Hampson P, Lord JM (2013) Depressive symptoms are associated with reduced monocyte neutrophil function in hip fracture patients. Brain Behav Immun 33:173–182.  https://doi.org/10.1016/j.bbi.2013.07.004CrossRefGoogle Scholar
  51. Duggal NA, Beswetherick A, Upton J, Hampson P, Phillips AC, Lord JM (2014a) Depressive symptoms in hip fracture patients are associated with reduced monocyte superoxide production. Exp Gerontol 54:27–34.  https://doi.org/10.1016/j.exger.2014.01.028CrossRefGoogle Scholar
  52. Duggal NA, Upton J, Phillips AC, Hampson P, Lord JM (2014b) Depressive symptoms post hip fracture in older adults are associated with phenotypic and functional alterations in T cells. Immun Ageing 11:25.  https://doi.org/10.1186/s12979-014-0025-5CrossRefGoogle Scholar
  53. Duggal NA, Upton J, Phillips AC, Lord JM (2016) Development of depressive symptoms post hip fracture is associated with altered immunosuppressive phenotype in regulatory T and B lymphocytes. Biogerontology 17:229–239.  https://doi.org/10.1007/s10522-015-9587-7CrossRefGoogle Scholar
  54. Dunn RR, Fierer N, Henley JB, Leff JW, Menninger HL (2013) Home life: factors structuring the bacterial diversity found within and between homes. PLoS One 8:e64133.  https://doi.org/10.1371/jornal.pone.0064133CrossRefGoogle Scholar
  55. Duramad P, Harley K, Lipsett M, Bradman A, Eskenazi B, Holland NT et al (2006) Early environmental exposures and intracelular Th1/Th2 cytokine profiles in 24-month-old children living in an agricultural area. Environ Health Perspect 114:1916–1922CrossRefGoogle Scholar
  56. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M et al (2005) Diversity of the human intestinal microbial flora. Science 308:1635–1638CrossRefGoogle Scholar
  57. Ekblom-Bak E, Ekblom B, Vikström M, De Faire U, Hellénius M-L (2014) The importance of non-exercise physical activity for cardiovascular health and longevity. Br J Sports Med 48:233–238.  https://doi.org/10.1136/bjsports-2012-092038CrossRefGoogle Scholar
  58. El Aidy S, Hooiveld G, Tremaroli V, Bäckhed F, Kleerebezem M (2013) The gut microbiota and mucosal homeostasis: colonized at birth ora t adulthood, does it matter? Gut Microbes 4:118–124.  https://doi.org/10.4161/gmic.23362CrossRefGoogle Scholar
  59. Ershler WB (1993) Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc 41:176–181CrossRefGoogle Scholar
  60. Fleg JL, Cooper LS, Borlaug BA, Haykowsky MJ, Kraus WE, Levine BD et al (2015) Exercise training as therapy for heart failure: current status and future directions. Circ Heart Fail 8:209–220.  https://doi.org/10.1161/CIRCHEARTFAILURE.113.001420CrossRefGoogle Scholar
  61. Ford BN, Yolken RH, Dickerson FB, Teague TK, Irwin MR, Paulus MP et al (2018) Reduced immunity to measles in adults with major depressive disorder. Psychol Med 19:1–7.  https://doi.org/10.1017/S0033291718000661CrossRefGoogle Scholar
  62. Fujimura KE, Johnson CC, Ownby DR, Cox MJ, Brodie EL, Havstad SL et al (2010) Man’s best friend? The effect of pet ownership on house dust microbial communities. J Allergy Clin Immunol 126:410–412.  https://doi.org/10.1016/j.jaci.2010.05.042CrossRefGoogle Scholar
  63. Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D et al (2016) Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med 22:1187–1191.  https://doi.org/10.1038/nm.4176CrossRefGoogle Scholar
  64. Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A, Bridonneau C et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31:677–689.  https://doi.org/10.1016/j.immuni.2009.08.020CrossRefGoogle Scholar
  65. Gaesser GA (2007) Exercise for prevention and treatment of cardiovascular disease, type 2 diabetes, and metabolic syndrome. Curr Diab Rep 7:14–19CrossRefGoogle Scholar
  66. Gensollen T, Iyer SS, Kasper DL, Bumberg RS (2016) How colonization by microbiota in early life shapes the immune system. Science 352:539–544.  https://doi.org/10.1126/science.aad9378CrossRefGoogle Scholar
  67. Gern JE, Reardon CL, Hoffjan S, Nicolae D, Li Z, Roberg KA et al (2004) Effects of dog ownership and genotype on imune development and atopy in infancy. J Allergy Clin Immunol 113:307–314CrossRefGoogle Scholar
  68. Geuking MB, Cahenzli J, Lawson MA, Ng DC, Slack E, Hapfelmeier S et al (2011) Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34:794–806.  https://doi.org/10.1016/j.immunol.2011.03.021CrossRefGoogle Scholar
  69. Ginhoux F, Jung S (2014) Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14:392–404.  https://doi.org/10.1038/nri3671CrossRefGoogle Scholar
  70. Gordon HA, Bruckner-Kardoss E, Staley TE, Wagner M, Wostmann BS (1966) Characteristics of the germfree rat. Acta Anat 64:367–389CrossRefGoogle Scholar
  71. Gouin JP, Glaser R, Malarkey WB, Beversdorf D, Kiecolt-Glaser J (2012) Chronic stress, daily stressors, and circulating inflammatory markers. Health Psychol 31:264–268.  https://doi.org/10.1037/a0025536CrossRefGoogle Scholar
  72. Greer JB, O’Keefe SJ (2011) Microbial induction of immunity, inflammation, and cancer. Front Physiol 1:168.  https://doi.org/10.3389/fphys.2010.00168CrossRefGoogle Scholar
  73. Grüber C, Keil T, Kulig M, Roll S, Wahn U, Wahn V et al (2008) History of respiratory infections in the first 12 yr among children from a birth cohort. Pediatr Allergy Immunol 19:505–512.  https://doi.org/10.1111/j.1399-3038.2007.00688.xCrossRefGoogle Scholar
  74. Hagendorens MM, Bridts CH, Lauwers K, van Nuijs S, Ebo DG, Vellinga A et al (2005) Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO study). Clin Exp Allergy 35:733–740CrossRefGoogle Scholar
  75. Hand D, Wallis C, Colyer A, Penn CW (2013) Pyrosequencing the canine faecal microbiota: breadth and depth of biodiversity. PLoS One 8:e53115.  https://doi.org/10.1371/jornal.pone.0053115CrossRefGoogle Scholar
  76. Hatakka K, Piirainen L, Pohjavuori S, Poussa T, Savilahti E, Korpela R (2010) Factors associated with acute respiratory illness in day care children. Scand J Infect Dis 42:704–711.  https://doi.org/10.3109/00365548.2010.483476CrossRefGoogle Scholar
  77. Heinrich J, Gehring U, Douwes J, Koch A, Fahlbusch B, Bischof W et al (2001) Pets and vermin are associated with high endotoxin levels in house dust. Clin Exp Allergy 31:1839–1845CrossRefGoogle Scholar
  78. Herbert TB, Cohen S (1993) Depression and immunity: a meta-analytic review. Psychol Bull 113:472–486CrossRefGoogle Scholar
  79. Hesselman B, Aberg N, Aberg B, Eriksson B, Bjorksten B (1999) Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy 29:611–617CrossRefGoogle Scholar
  80. Hodes GE, Kana V, Menard C, Merad M, Russo SJ (2015) Neuroimmune mechanisms of depression. Nat Neurosci 18:1386–1393.  https://doi.org/10.1038/nn.4113CrossRefGoogle Scholar
  81. Horner AA (2006) Toll-like receptor ligands and atopy: a coin with at least two sides. J Allergy Clin Immunol 117:1133–1140CrossRefGoogle Scholar
  82. Houghteling PD, Walker WA (2015) Why is initial bacterial colonization of the intestine important to the infant’s and child’s health? J Pediatr Gastroenterol Nutr 60:294–307.  https://doi.org/10.1097/MPG.0000000000000597CrossRefGoogle Scholar
  83. Irwin M (2002) Psychoneuroimmunology of depression: clinical implications. Brain Behav Immun 16:1–16CrossRefGoogle Scholar
  84. Irwin MR, Levin MJ, Carrillo C, Olmstead R, Lucko A, Lang N et al (2011) Major depressive disorder and immunity to varicella-zoster virus in the elderly. Brain Behav Immun 25:759–766.  https://doi.org/10.1016/j.bbi.2011.02.001CrossRefGoogle Scholar
  85. Ise W (2016) Development and function of follicular helper T cells. Biosci Biotechnol Biochem 80:1–6.  https://doi.org/10.1080/09168451.2015.1056512CrossRefGoogle Scholar
  86. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U et al (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–498.  https://doi.org/10.1016/j.cell.2009.09.033CrossRefGoogle Scholar
  87. Janeway CA Jr (1992) The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 13:11–16CrossRefGoogle Scholar
  88. Jenssen J, Cardiello F, Baun MM (1996) Avian companionship in alleviation of depression, loneliness, and low morale of older adults in skilled rehabilitation units. Psychol Rep 78:339–348CrossRefGoogle Scholar
  89. Johansson MA, Sjogren YM, Persson JO, Nilsson C, Sverremark-Ekstrom E (2011) Early colonization with a group of Lactobacilli decreases the risk for allergy at five years of age despite allergic heredity. PLoS One 6:e23031.  https://doi.org/10.1371/journal.pone.0023031CrossRefGoogle Scholar
  90. Johnson CC, Ownby DR (2016) Allergies and asthma: do atopic disorders result from inadequate immune homeostasis arising from infant gut dysbiosis? Expert Rev Clin Immunol 12:379–388.  https://doi.org/10.1586/1744666X.2016.1139452CrossRefGoogle Scholar
  91. Johnson CC, Ownby DR (2017) The infant gut bacterial microbiota and risk of pediatric asthma and allergic diseases. Transl Res 179:60–70.  https://doi.org/10.1016/j.trsl.2016.06.010CrossRefGoogle Scholar
  92. Kalliomaki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E (2001) Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 107:129–134CrossRefGoogle Scholar
  93. Kang J-W, Kim S-J, Cho H-I, Lee S-M (2015) DAMPs activating innate imune responses in sepsis. Ageing Res Rev 24:54–65.  https://doi.org/10.1016/j.arr.2015.03.003CrossRefGoogle Scholar
  94. Keylock KT, Lowder T, Leifheit KA, Cook M, Mariani RA, Ross K et al (2007) Higher antibody, but not cell-mediated, responses to vaccination in high physically fit elderly. J Appl Physiol 102:1090–1098CrossRefGoogle Scholar
  95. Kiecolt-Glaser JK, Dura JR, Speicher CE, Trask OJ, Glaser R (1991) Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosom Med 53:345–362CrossRefGoogle Scholar
  96. Klaasen HL, van der Heijden PJ, Stok W, Poelma FG, Koopman JP, van den Brink ME et al (1993) Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice. Infect Immun 61:303–306Google Scholar
  97. Kohut ML, Cooper MM, Nickolaus MS, Russell DR, Cunnick JE (2002) Exercise and psychosocial factors modulate immunity to influenza vaccine in elderly individuals. J Gerontol A Biol Sci Med Sci 57:M557–M5762CrossRefGoogle Scholar
  98. Krause-Parello CA, Tychowski J, Gonzalez A, Boyd Z (2012) Human-canine interaction: exploring stress indicator response patterns of salivary cortisol and immunoglobulin A. Res Theory Nurs Pract 26:25–40CrossRefGoogle Scholar
  99. Kronfol Z (1983) Cancer and depression. Br J Psychiatry 142:309CrossRefGoogle Scholar
  100. Kumar S (2018) Natural killer cell cytotoxicity and its regulation by inhibitory receptors. Immunology.  https://doi.org/10.1111/imm.12921CrossRefGoogle Scholar
  101. Lamichhane A, Azegamia T, Kiyonoa H (2014) The mucosal immune system for vaccine development. Vaccine 32:6711–6723.  https://doi.org/10.1016/j.vaccine.2014.08.089CrossRefGoogle Scholar
  102. Levin AM, Sitarik AR, Havstad SL, Fujimura KE, Wegienka G, Cassidy-Bushrow AE et al (2016) Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity. Sci Rep 6:31775.  https://doi.org/10.1038/srep31775CrossRefGoogle Scholar
  103. Litonjua AA, Milton DK, Celedon JC, Ryan L, Weiss ST, Gold DR (2002) A longitudinal analysis of wheezing in young children: the independent effects of early life exposure to house dust endotoxin, allergens, and pets. J Allergy Clin Immunol 110:736–742CrossRefGoogle Scholar
  104. Lodrup Carlsen KC, Roll S, Carlsen KH, Mowinckel P, Wijga AH, Brunekreef B et al (2012) Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts. PLoS One 7:e43214.  https://doi.org/10.1371/journal.pone.0043214CrossRefGoogle Scholar
  105. Lynch SV, Wood RA, Boushey H, Bacharier LB, Bloomberg GR, Kattan M et al (2014) Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. J Allergy Clin Immunol 134:593–601.  https://doi.org/10.1016/j.jaci.2014.04.018CrossRefGoogle Scholar
  106. Macpherson AJ, Harris NL (2004) Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4:478–485CrossRefGoogle Scholar
  107. Maes M (2011) Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuro-Psychopharmacol Biol Psychiatry 35:664–675.  https://doi.org/10.1016/j.pnpbp.2010.06.014CrossRefGoogle Scholar
  108. Maggi E, Del Prete G, Macchia D, Parronchi P, Tiri A, Chrétien I et al (1988) Profiles of lymphokine activities and helper function for IgE in human T cell clones. Eur J Immunol 18:1045–1050CrossRefGoogle Scholar
  109. Makino H, Kushiro A, Ishikawa E, Kubota H, Gawad A, Sakai T et al (2013) Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant’s microbiota. PLoS One 8:e78331.  https://doi.org/10.1371/jornal.pone.0078331CrossRefGoogle Scholar
  110. Marshall GD, Agarwal SK, Lloyd C, Cohen L, Henninger EM, Morris GJ (1998) Cytokine dysregulation associated with exam stress in healthy medical students. Brain Behav Immun 12:297–307CrossRefGoogle Scholar
  111. Martín R, Jiménez E, Heilig H, Fernández L, Marín ML, Zoetendal EG et al (2009) Isolation of Bifidobacteria from breast milk and assessment of the Bifidobacterial population by PCR-denaturing gradient gel electrophoresis and quantitative real-time PCR. Appl Environ Microbiol 75:965–969.  https://doi.org/10.1128/AEM.02063-08CrossRefGoogle Scholar
  112. Matzinger P (1994) Tolerance, danger and the extended family. Annu Rev Immunol 12:991–1045CrossRefGoogle Scholar
  113. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bactéria directs maturation of the host immune system. Cell 122:107–118CrossRefGoogle Scholar
  114. McBrien JB, Kumar NA, Silvestri G (2018) Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication. Eur J Immunol.  https://doi.org/10.1002/eji.201747172CrossRefGoogle Scholar
  115. McEwen BS (2012) Brain on stress: how the social environment gets under the skin. Proc Natl Acad Sci U S A 109(Suppl 2):17180–17185.  https://doi.org/10.1073/pnas.1121254109CrossRefGoogle Scholar
  116. Middelbos IS, Vester Boler BM, Qu A, White BA, Swanson KS, Fahey GC Jr (2010) Phylogenetic characterization of fecal microbial communities of dogs fed diets with or without supplemental dietary fiber using 454 pyrosequencing. PLoS One 5:e9768.  https://doi.org/10.1371/journal.pone.0009768CrossRefGoogle Scholar
  117. Mitchell G, Isberg RR (2017) Innate immunity to intracelular pathogens: balancing microbial elimination and inflammation. Cell Host Microbe 22:166–175.  https://doi.org/10.1016/j.chom.2017.07.005CrossRefGoogle Scholar
  118. Mohr A, Malhotra R, Mayer G, Gorochov G, Miyara M (2018) Human FOXP3+ T regulatory cell heterogeneity. Clin Transl Immunology:e1005.  https://doi.org/10.1002/cti.1005
  119. Monda V, Villan I, Messina A, Valenzano A, Esposito T, Moscatelli F et al (2017) Exercise modifies the gut microbiota with positive health effects. Oxidative Med Cell Longev 2017:3831972.  https://doi.org/10.1155/2017/3831972CrossRefGoogle Scholar
  120. Mora S, Cook N, Buring JE, Ridker PM, Lee IM (2007) Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation 116:2110–2118CrossRefGoogle Scholar
  121. Morey JN, Boggero IA, Scott AB, Segerstrom SC (2015) Current directions in stress and human immune function. Curr Opin Psychol 5:13–17CrossRefGoogle Scholar
  122. Moroda T, Kawachi Y, Iiai T, Tsukahara A, Suziki S, Tada T et al (1997) Self-reactive forbidden clones are confined to pathways of intermidate T-cell receptor cell differentiation even under immunosuppressive conditions. Immunology 91:88–94CrossRefGoogle Scholar
  123. Mosconi I, Geuking MB, Zaiss MM, Massacand JC, Aschwanden C, Kwong Chung CK et al (2013) Intestinal bacteria induce TSLP to promote mutualistic T-cell responses. Mucosal Immunol 6:1157–1167.  https://doi.org/10.1038/mi.2013.12CrossRefGoogle Scholar
  124. Murray CS, Tannock GW, Simon MA, Harmsen HJ, Welling GW, Custovic A et al (2005) Fecal microbiota in sensitized wheezy and non-sensitized non-wheezy children: a nested case–control study. Clin Exp Allergy 35:741–745CrossRefGoogle Scholar
  125. Musselman DL, Evans DL, Nemeroff CB (1998) The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 55:580–592CrossRefGoogle Scholar
  126. Nakata A, Irie M, Takahasi M (2011) Psychological distress, depressive symptoms, and cellular immunity among healthy individuals: a 1-year prospective study. Int J Psychophysiol 81:191–197.  https://doi.org/10.1016/j.ijpsycho.2011.06.009CrossRefGoogle Scholar
  127. Nakayama J, Kobayashi T, Tanaka S, Korenori Y, Tateyama A, Sakamoto N et al (2011) Aberrant structures of fecal bacterial community in allergic infants profiled by 16S rRNA gene pyrosequencing. FEMS Immunol Med Microbiol 63:397–406.  https://doi.org/10.1111/j.1574-695X.2011.00872.xCrossRefGoogle Scholar
  128. Nermes M, Niinivirta K, Nylund L, Laitinen K, Matomäki J, Salminen S et al (2013) Perinatal pet exposure, faecal microbiota, and wheezy bronchitis: is there a connection? ISRN Allergy 2013:827934.  https://doi.org/10.1155/2013/827934CrossRefGoogle Scholar
  129. Newburg DS, Walker WA (2007) Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res 61:2–8CrossRefGoogle Scholar
  130. Nie Y, Yang D, Oppenhem JJ (2016) Alarmins and antitumor immunity. Clin Ther 38:1042–1053.  https://doi.org/10.1016/j.clinthera.2016.03.021CrossRefGoogle Scholar
  131. Nimmo MA, Leggate M, Viana JL, King JA (2013) The effect of physical activity on mediators of inflammation. Diabetes Obes Metab 15(Suppl 3):51–60.  https://doi.org/10.1111/dom.12156CrossRefGoogle Scholar
  132. Nylund L, Satokari R, Nikkilä J, Rajilic-Stojanovic M, Kalliomäki M, Isolauri E et al (2013) Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiol 13:12.  https://doi.org/10.1186/1471-2180-13-12CrossRefGoogle Scholar
  133. O’Keefe SJ, Ou J, Aufreiter S, O’Connor D, Sharma S, Sepulveda J et al (2009) Products of the colonic microbiota mediate the effects of diet on colon cancer risk. J Nutr 139:2044–2048.  https://doi.org/10.3945/jn.109.104380CrossRefGoogle Scholar
  134. Odendaal JS (2000) Animal-assisted therapy - magic or medicine? J Psychosom Res 49:275–280CrossRefGoogle Scholar
  135. Odendaal JS, Meintjes RA (2003) Neurophysiological correlates of affiliative behaviour between humans and dogs. Vet J 165:296–301CrossRefGoogle Scholar
  136. Oh C, Lee K, Cheong Y, Lee SW, Park SY, Song CS et al (2015) Comparison of the oral microbiomes of canines and their owners using next-generation sequencing. PLoS One 10:e0131468.  https://doi.org/10.1371/journal.pone.0131468CrossRefGoogle Scholar
  137. Ownby DR, Johnson CC, Peterson EL (2002) Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 288:963–972CrossRefGoogle Scholar
  138. Padgett DA, Glaser R (2003) How stress influences the immune response. Trends Immunol 24:444–448CrossRefGoogle Scholar
  139. Parker W (2014) The “hygiene hypothesis” for allergic disease is a misnomer. Br Med J 348:g5267.  https://doi.org/10.1136/bmj.g5267CrossRefGoogle Scholar
  140. Parslow RA, Jorm AF (2003) Pet ownership and risk factors for cardiovascular disease: another look. Med J Aust 17:466–468CrossRefGoogle Scholar
  141. Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A (2005) Human immunosenescence: is it infectious? Immunol Rev 205:257–268CrossRefGoogle Scholar
  142. Peel E, Douglas M, Parry O, Lawton J (2010) Type 2 diabetes and dog walking: patients’ longitudinal perspectives about implementing and sustaining physical activity. Br J Gen Pract 60:570–577.  https://doi.org/10.3399/bjgp10X515061CrossRefGoogle Scholar
  143. Pelucchi C, Galeone C, Bach JF, La Vecchia C, Chatenoud L (2013) Pet exposure and risk of atopic dermatitis at the pediatric age: a meta-analysis of birth cohort studies. J Allergy Clin Immunol 132:616–622.  https://doi.org/10.1016/j.jaci.2013.04.009CrossRefGoogle Scholar
  144. Penders J, Stobberingh EE, van den Brandt PA, Thijs C (2007a) The role of the intestinal microbiota in the development of atopic disorders. Allergy 62:1223–1236CrossRefGoogle Scholar
  145. Penders J, Thijs C, van den Brandt PA, Kummeling I, Snijders B, Stelma F et al (2007b) Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 56:661–667CrossRefGoogle Scholar
  146. Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S et al (2013) Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol 132:601–607.  https://doi.org/10.1016/j.jaci.2013.05.043CrossRefGoogle Scholar
  147. Perez PF, Doré J, Leclerc M, Levenez F, Benyacoub J, Serrant P et al (2007) Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics 119:e724–e732CrossRefGoogle Scholar
  148. Peters RL, Allen KJ, Dharmage SC, Lodge CJ, Koplin JJ, Ponsonby AL et al (2015) Differential factors associated with challenge-proven food allergy phenotypes in a population cohort of infants: a latent class analysis. Clin Exp Allergy 45:953–963.  https://doi.org/10.1111/cea.12478CrossRefGoogle Scholar
  149. Pradeu T, Du Pasquier L (2018) Immunological memory: what’s in a name? Immunol Rev 283:7–20.  https://doi.org/10.1111/imr.12652CrossRefGoogle Scholar
  150. Pryde SE, Duncan SH, Hold GL, Stewart CS, Flint HJ (2002) The microbiology of butyrate formation in the human colon. FEMS Microbiol Lett 217:133–139CrossRefGoogle Scholar
  151. Rakoff-Nahoum S, Medzhitov R (2008) Innate immune recognition of the indigenous microbial flora. Mucosal Immunol 1(Suppl 1):S10–S14.  https://doi.org/10.1038/mi.2008.49CrossRefGoogle Scholar
  152. Remes ST, Castro-Rodriguez JA, Holberg CJ, Martinez FD, Wright AL (2001) Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy. J Allergy Clin Immunol 108:509–515CrossRefGoogle Scholar
  153. Riedler J, Braun-Fahrländer C, Eder W, Schreuer M, Waser M, Maisch S et al (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129–1133CrossRefGoogle Scholar
  154. Rohleder N (2012) Acute and chronic stress induced changes in sensitivity of peripheral inflammatory pathways to the signals of multiple stress systems — 2011 Curt Richter Award Winner. Psychoneuroendocrinology 37:307–316.  https://doi.org/10.1016/j.psyneuen.2011.12.015CrossRefGoogle Scholar
  155. Roponen M, Hyvärinen A, Hirvonen MR, Keski-Nisula L, Pekkanen J (2005) Change in IFN-gamma-producing capacity in early life and exposure to environmental microbes. J Allergy Clin Immunol 116:1048–1052CrossRefGoogle Scholar
  156. Rosenblat JD, Cha DS, Mansur RB, McIntyre RS (2014) Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 53:23–34.  https://doi.org/10.1016/j.pnpbp.2014.01.013CrossRefGoogle Scholar
  157. Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z et al (2006) Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 212:8–27CrossRefGoogle Scholar
  158. Sallam N, Laher I (2016) Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases. Oxidative Med Cell Longev 2016:7239639.  https://doi.org/10.1155/2016/7239639CrossRefGoogle Scholar
  159. Scarpellini E, Ianiro G, Attili F, Bassanelli C, De Santis A, Gasbarrini A (2015) The human gut microbiota and virome: potential therapeutic implications. Dig Liver Dis 47:1007–1012.  https://doi.org/10.1016/j.dld.2015.07.008CrossRefGoogle Scholar
  160. Schaub B, Liu J, Höppler S, Schleich I, Huehn J, Olek S et al (2009) Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol 123:774–782.  https://doi.org/10.1016/j.jaci.2009.01.056CrossRefGoogle Scholar
  161. Schippa S, Conte MP (2014) Dysbiotic events in gut microbiota: impact on human health. Nutrients 6:5786–5805.  https://doi.org/10.3390/nu6125786CrossRefGoogle Scholar
  162. Schmidt ME, Varga SM (2018) The CD8 T cell response to respiratory virus infection. Front Immunol 9:678.  https://doi.org/10.3389/fimmu.2018.00678CrossRefGoogle Scholar
  163. Schuijs MJ, Willart MA, Vergote K, Gras D, Deswarte K, Ege MJ et al (2015) Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science 349:1106–1110.  https://doi.org/10.1126/science.aac6623CrossRefGoogle Scholar
  164. Schuler PB, Leblanc PA, Marzilli TS (2003) Effect of physical activity on the production of specific antibody in response to the 1998-99 influenza virus vaccine in older adults. J Sports Med Phys Fitness 43:404Google Scholar
  165. Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire AM et al (2015) Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 349:993–997.  https://doi.org/10.1126/science.aaa9420CrossRefGoogle Scholar
  166. Segerstrom SC, Miller GE (2004) Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 130:601–630CrossRefGoogle Scholar
  167. Shephard RJ, Balady GJ (1999) Exercise as cardiovascular therapy. Circulation 99:963–972CrossRefGoogle Scholar
  168. Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11:762–774.  https://doi.org/10.1038/nri3070CrossRefGoogle Scholar
  169. Shibata A, Oka K, Inoue S, Christian H, Kitabatake Y, Shimomitsu T (2012) Physical activity of Japanese older adults who own and walk dogs. Am J Prev Med 43:429–433CrossRefGoogle Scholar
  170. Simpson A (2010) Effect of household pet ownership on infant immune response and subsequent sensitization. J Asthma Allergy 3:131–137.  https://doi.org/10.2147/JAA.S6958CrossRefGoogle Scholar
  171. Singh NK, Riley TP, Baker SCB, Borrman T, Weng Z, Baker BM (2017) Emerging concepts in TCR specificity: rationalizing and (maybe) predicting outcomes. J Immunol 199:2203–2213.  https://doi.org/10.4049/jimmunol.1700744CrossRefGoogle Scholar
  172. Sitarik AR, Havstad S, Levin AM, Lynch SV, Fujimura KE, Ownby DR et al (2018) Dog introduction alters the home dust microbiota. Indoor Air.  https://doi.org/10.1111/ina.12456CrossRefGoogle Scholar
  173. Sjögren YM, Jenmalm MC, Böttcher MF, Björkstén B, Sverremark-Ekstrom E (2009) Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin Exp Allergy 39:518–526.  https://doi.org/10.1111/j.1365-2222.2008.03156.xCrossRefGoogle Scholar
  174. Smith TP, Kennedy SL, Fleshner M (2004) Influence of age and physical activity on the primary in vivo antibody and T cell-mediated responses in men. J Appl Physiol 97:491–498CrossRefGoogle Scholar
  175. Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G, Berg-Lyons D et al (2013) Cohabiting family members share microbiota with one another and with their dogs. elife 2:e00458.  https://doi.org/10.7554/eLife.00458CrossRefGoogle Scholar
  176. Sorrells SF, Sapolsky RM (2007) An inflammatory review of glucocorticoid actions in the CNS. Brain Behav Immun 21:259–272CrossRefGoogle Scholar
  177. Spor A, Koren O, Ley R (2011) Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol 9:279–290.  https://doi.org/10.1038/nrmicro2540CrossRefGoogle Scholar
  178. Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V, Murray SE et al (2016) Innate immunity and asthma risk in Amish and Hutterite farm children. N Engl J Med 375:411–421.  https://doi.org/10.1056/NEJMoa1508749CrossRefGoogle Scholar
  179. Steptoe A, Hamer M, Chida Y (2007) The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 21:901–912CrossRefGoogle Scholar
  180. Stojanovich L, Marisavljevich D (2008) Stress as a trigger nof autoimmune disease. Autoimmun Rev 7:209–213.  https://doi.org/10.1016/j.autrev.2007.11.007CrossRefGoogle Scholar
  181. Strachan DP (1989) Hay fever, hygiene and household size. Br Med J 299:1259–1260CrossRefGoogle Scholar
  182. Sturgeon A, Stull JW, Costa MC, Weese JS (2013) Metagenomic analysis of the canine oral cavity as revealed by high-throughput pyrosequencing of the 16S rRNA gene. Vet Microbiol 162:891–898.  https://doi.org/10.1016/j.vetmic.2012.11.018CrossRefGoogle Scholar
  183. Szostak J, Laurant P (2011) The forgotten face of regular physical exercise: a ‘natural’ anti-atherogenic activity. Clin Sci 121:91–106.  https://doi.org/10.1042/CS20100520CrossRefGoogle Scholar
  184. Takeda A, Sasaki N, Miyasaka M (2017) The molecular cues regulating immune cell trafficking. Proc Jpn Acad Ser B Phys Biol Sci 93:183–195.  https://doi.org/10.2183/pjab.93.012CrossRefGoogle Scholar
  185. Tartey S, Takeuchi O (2017) Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells. Int Rev Immunol 36:57–73.  https://doi.org/10.1080/08830185.2016.1261318CrossRefGoogle Scholar
  186. Thorpe RJ Jr, Kreisle RA, Glickman LT, Simonsick EM, Newman AB, Kritchevsky S (2006) Physical activity and pet ownership in year 3 of the Health ABC study. J Aging Phys Act 14:154–168CrossRefGoogle Scholar
  187. Touzot M, Grandclaudon M, Cappuccio A, Satoh T, Martinez-Cingolani C, Servant N, Manel N, Soumelis V (2014) Combinatorial flexibility of cytokine function during human T helper cell differentiation. Nat Commun 5:3987.  https://doi.org/10.1038/ncomms4987CrossRefGoogle Scholar
  188. Tse K, Horner AA (2008) Allergen tolerance versus the allergic march: the hygiene hypothesis revisited. Curr Allergy Asthma Rep 8:475–483CrossRefGoogle Scholar
  189. Tun HM, Konya T, Takaro TK, Brook JR, Chari R, Field CJ et al (2017) Exposure to household furry pets influences the gut microbiota of infants at 3-4 months following various birth scenarios. Microbiome 5:40.  https://doi.org/10.1186/s40168-017-0254-xCrossRefGoogle Scholar
  190. Turner JE, Brum PC (2017) Does regular exercise counter T cell immunosenescence reducing the risk of developing cancer and promoting successful treatment of malignancies? Oxidative Med Cell Longev 2017:4234765.  https://doi.org/10.1155/2017/4234765CrossRefGoogle Scholar
  191. Vael C, Vanheirstraeten L, Desager KN, Goossens H (2011) Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma. BMC Microbiol 11:68.  https://doi.org/10.1186/1471-2180-11-68CrossRefGoogle Scholar
  192. Vebo HC, Sekelja M, Nestestog R, Storro O, Johnsen R, Oien T et al (2011) Temporal development of the infant gut microbiota in IgE sensitized and non-sensitized children determined by the GA-map infant array. Clin Vaccine Immunol 18:1326–1335.  https://doi.org/10.1128/CVI.00062-11CrossRefGoogle Scholar
  193. Viau R, Arsenault-Lapierre G, Fecteau S, Champagne N, Walker CD, Lupien S (2010) Effect of service dogs on salivary cortisol secretion in autistic children. Psychoneuroendocrinology 35:11871193.  https://doi.org/10.1016/j.psyneuen.2010.02.004CrossRefGoogle Scholar
  194. Villeneuve C, Kou HH, Eckermann H, Palkar A, Anderson LG, McKenney EA et al (2018) Evolution of the hygiene hypothesis into biota alteration theory: what are the paradigms and where are the clinical applications? Microbes Infect 20:147–155.  https://doi.org/10.1016/j.micinf.2017.11.001CrossRefGoogle Scholar
  195. Vitlic A, Lord JM, Philips AC (2014) Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system. Age (Dordr) 36:1169–1185.  https://doi.org/10.1007/s11357-014-9631-6CrossRefGoogle Scholar
  196. Walling BL, Kim M (2018) LFA-1 in T cell migration and differentiation. Front Immunol 9:952.  https://doi.org/10.3389/fimmu.2018.00952CrossRefGoogle Scholar
  197. Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC et al (2011) Position statement. Part one: Immune function and exercise. Exerc Immunol Rev 17:6–63Google Scholar
  198. Wegienka G, Johnson CC, Havstad S, Ownby DR, Zoratti EM (2010) Indoor pet exposure and the outcomes of total IgE and sensitization at age 18 years. J Allergy Clin Immunol 126:274–279.  https://doi.org/10.1016/j.jaci.2010.05.001CrossRefGoogle Scholar
  199. Wegienka G, Johnson CC, Havstad S, Ownby DR, Nicholas C, Zoratti EM (2011) Lifetime dog and cat exposure and dog-and cat-specific sensitization at age 18 years. Clin Exp Allergy 41:979–986.  https://doi.org/10.1111/j.1365-2222.2011.03747.xCrossRefGoogle Scholar
  200. Weisse CS (1992) Depression and immunocompetence: a review of the literature. Psychol Bull 111:475–489CrossRefGoogle Scholar
  201. West CE, Jenmalm MC, Prescott SL (2014) The gut microbiota and its role in the development of allergic disease: a wider perspective. Clin Exp Allergy 45:43–53.  https://doi.org/10.1111/cea.12332CrossRefGoogle Scholar
  202. Wierenga EA, Snoek M, Jansen HM, Bos JD, van Lier RA, Kapsenberg ML (1991) Human atopen-specific types 1 and 2 T helper cell clones. J Immunol 1(147):2942–2949Google Scholar
  203. Wolf JM, Miller GE, Chen E (2008) Parent psychological states predict changes in inflammatory markers in children with asthma and healthy children. Brain Behav Immun 22:433–441CrossRefGoogle Scholar
  204. Yakeu G, Butcher L, Isa S, Webb R, Roberts AW, Thomas AW et al (2010) Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: roles of PPARγ and Th2 cytokines. Atherosclerosis 212:668–673.  https://doi.org/10.1016/j.atherosclerosis.2010.07.002CrossRefGoogle Scholar
  205. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M et al (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227.  https://doi.org/10.1038/nature11053CrossRefGoogle Scholar
  206. Yuseff MI, Pierobon P, Reversat A, Lennon-Duménil AM (2013) How B cells capture, process and present antigens: a crucial role for cell polarity. Nat Rev Immunol 13:475–486.  https://doi.org/10.1038/nri3469CrossRefGoogle Scholar
  207. Zhao Q, Elson CE (2018) Adaptive immune education by gut microbiota antigens. Immunology 154:28–37.  https://doi.org/10.1111/imm.12896CrossRefGoogle Scholar
  208. Zhao W, Ukawa S, Kawamura T, Wakai K, Andon M, Tsushita K et al (2015) Health benefits of daily walking on mortality among younger-elderly men with or without major critical diseases in the new integrated suburban seniority investigation project: a prospective cohort study. J Epidemiol 25:609–616.  https://doi.org/10.2188/jea.JE20140190CrossRefGoogle Scholar
  209. Zharkova O, Celhar T, Cravens PD, Satterthwaite AB, Fairhurst AM, Davis LS (2017) Pathways leading to an immunological disease: systemic lupus erythematosus. Rheumatology 56(Suppl. 1):i55–i66.  https://doi.org/10.1093/rheumatology/kew427CrossRefGoogle Scholar
  210. Zorrilla EP, Luborsky L, McKay JR, Rosenthal R, Houldin A, Tax A et al (2001) The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun 15:199–226CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Allergy & Clinical ImmunologyCova da Beira University Hospital CentreCovilhãPortugal
  2. 2.NuESA – Health & Environment Study Group, Faculty of Health SciencesUniversity of Beira InteriorCovilhãPortugal

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