Abstract
Immunosenescence has been envisaged as a situation in which the specific immune system deteriorates with age, while the innate immunity is negligibly affected and, in some cases, almost upregulated. Ageing represents a state of paradox where chronic inflammation is associated with declining immune responses. This peculiar finding, known as inflammageing, is mainly sustained by cells of the innate immunity. One of the key constituents of the innate immune system are monocytes. Therefore, although the age-related changes in the specific immunity are commonly considered the hallmarks of immunosenescence, the central role of the complex remodelling of first line defence cells, such as monocytes, is gradually emerging. For example, chemotaxis and phagocytosis, as well as antigen processing and presentation, are depressed, whereas cell activation and the secretion of inflammatory cytokines, such as IL-1, IL-6, TNF, are markedly increased. Changes in the expression of functionally important cellular receptors on monocyte surface can also contribute to the modification of immune function characteristic of the elderly.
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References
Agrawal A, Agrawal S, Cao JN et al (2007) Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol 178:6912–6922
Albright JW, Albright JF (1994) Ageing alters the competence of the immune system to control parasitic infection. Immunol Lett 40:279–285
Anderson CF, Mosser DM (2002) A novel phenotype for an activated macrophage: the type 2 activated macrophage. J Leukoc Biol 72:101–106
Antonini JM, Roberts JR, Clarke RW, Yang HM et al (2001) Effect of age on respiratory defense mechanisms: pulmonary bacterial clearance in Fischer 344 rats after intratracheal instillation of Listeria monocytogenes. Chest 120:240–249
Ahluwalia N, Mastro AM, Ball R et al (2001) Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women. Mech Ageing Dev 122:1269–1279
Ashcroft GS, Horan MA, Ferguson MW et al (1998) Aging alters the inflammatory and endothelial cell adhesion molecule protiles during human cutaneous wound healing. Lab Invest 78:47–58
Bautmans L, Njemini R, Lambert M et al (2005) Circulating acute phase mediators and skeletal muscle performance in hospitalized geriatric patients. J Gerontol 60:361–367
Beutler B (2004) Inferences, questions and possibilities in Toll-like mceptor signaling. Nature 430:257–263
Boehmer ED, Goral J, Faunce DE, Kovacs EJ (2004) Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. J Leukoc Bio1 75:342–349
Boehmer ED, Meehan MJ, Cutro BT, Kovacs EJ (2005) Aging negativrly skews macrophage TLR2- and TLR4-mediated pro-inflammatory responses without affecting the IL-2-stimulated pathway. Mech Ageing Dev 126:1305–1313
Bondada S, Wu H, Robertson DA, Chelvarajan RL (2000) Accessory cell defect in unresponsiveness of neonates and aged to polysaccharide vaccines. Vaccine 19:557–565
Bradley SF, Kauffman CA (1990) Aging and the response to Salmonella infection. Exp Gerontol 25:75–80
Castle SC (2000) Clinical relevance of age related immune dysfunction. Clin Infect Dise 31:578–585
Chelvarajan RL, Collins SM, Van Willigen JM, Bondada S (2005) The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function. J Leukoc Biol 77:503–512
Chelvarajan RL, Liu Y, Popa D, Getchell ML et al (2006) Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages. J Leukoc Biol 79:1314–1327
Chinetti G, Fruchart JC, Staels B (2000) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 49:497–505
Chiricolo M, Morini MC, Mancini R et al (1995) Cell adhesion molecules CD11a and CD18 in blood monocytes in old age and the consequences for immunological dysfunction. Preliminary results. Gerontology 41:227–234
Clark RB (2002) The role of PPARs in inflammation and immunily. J Leukoc Biol 21:388–400
Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252
de Fougerolles AR, Qin X, Springer TA (1994) Characterization of the function of intercellular adhesion molecule (ICAM)-3 and comparison with ICAM-1 and ICAM-2 in immune responses. J Exp Med 179:619–629
Della Bella S, Bierti L, Presicce P et al (2007) Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol 122:220–228
del Pozo MA, Pulido R, Munoz C, Alvarez V et al (1994) Regulation of ICAM-3 (CD50) membrane expression on human neutrophils through proteolytic shedding mechanism. Eur J Immunol 24:2586–2594
De Martinis M, Modesti M, Loreto MF et al (2000) Adhesion molecules on peripheral blood lymphocyte subpopulations in the elderly. Life Sci 68:139–151
De Martinis M, Modesti M, Ginaldi L (2004) Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons. Immunol Cell Biol 82:415–420
DeVeale B, Brummet TL, Seroude L et al (2004) Immunity and aging: the enemy within? Aging Cell 3:195–208
Dillon S, Agrawal A, Van Dyke T et al (2004) A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol 172:4733–4743
Ding A, Hwang S, Schwab R (1994) Effect of aging on murine macrophages. Diminished response to IFNgamma for enhanced oxidative metabolism. J Immunol 153:2146–2152
Donnelly R P, Dickensheets H, Finbloom DS (1999) The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagacytes. J Interferon Cytokine Res 99:563–573
Donnini A, Argentati K, Mancini R et al (2002) Phenotype, antigen-presenting capacity, and migration of antigen-presenting cells in young and old age. Exp Gerontol 37:1097–1112
Elenkov IJ, Chrousos GP (2002) Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 966:290–303
Feart C, Pallet V, Boucheron C, Higueret D et al (2005) Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells. Eur J Endocrinol 152:449–458
Fernandez S, Jose P, Avdiushko MG et al (2004) Inhibition of IL-10 receptor function in alveolar macrophages by Toll-like receptor agonists. J Immunol 172:2613–2620
Fortunel NO, Hatzfeld A, Hatzfeld JA et al (2000) Transforming growth factor-β: pleiotropic role in the regulation of hematopoiesis. Blood 96:2022–2036
Franceschi C, Bonafe M, Valensin S et al (2000) Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine 18:1717–1720
Franceschi C, Bonafe M, Valensin S et al (2000) Inflammaging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
Franceschi C, Bonafè M (2003) Centenarians as a model of healthy aging. Biochem Soc Transact 31:457–461
Friedman G, Ben-Yehuda A, Dabach Y et al (1997) Scavanger receptor activiry and expression of apolipoprotein E mRNA in monocyte derived macrophages of young and old healthy men. Atherosclerosis 128:67–73
Gao JJ, Diesl V, Wittmann T et al (2002) Regulation of gene expression in mouse macrophages stimulated with bacterial CpG-DNA and lipopolysaccharide. J Leukoc Biol 72:1234–1245
Garg M, Luo W, Kaplan AM, Bondada S (1996) Cellular basis of decreased immune responses to pneumococcal vaccines in aged mice. Infect Immun 64:4456–4462
Geiger H, Van Zant G (2002) Thc aging of lympho-hematopoietic stem cells. Nat Immunol 3:329–333
Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82
Ginaldi L, De Martinis M, D’Ostilio A et al (2001) Changes in the expression of surface receptors on lymphocyte subsets in the elderly: quantitative flow cytometry analysis. Am J Hematol 67:63–72
Ginaldi L, De Martinis M, D’Ostilio A et al (1999) The immune system in the elderly. III. Innate immunity. Immunol Res 20:117–126
Ginaldi L, De Martinis M, Modesti M et al (2000) Immunophenotypical changes of T lymphocytes in the elderly. Gerontology 46:242–248
Ginaldi L, Matutes E, Farahat N et al (1996) Differential expression of T cell antigens in normal peripheral blood lymphocytes: a quantitative analysis by flow cytometry. J Clin Pathol 49:539–544
Ginaldi L, Sternberg H (2003) The immune system. In: Timiras PS (ed) Physiological basis of aging and geriatrics, 3rd edn. CRC Press, NY, pp 265–283
Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35
Gratchev A, Schledzewski K, Guillot P, Goerdt S (2001) Alternatively activated antigen-presenting cells: molecular repertoire, immune regulation, and healing. Skin Pharmacol Appl Skin Physiol 14:272–279
Greiwe JS, Cheng B, Rubin DC et al (2001) Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15:475–482
Hakim FT, Flomerfelt FA, Boyiadiis M, Gress RE (2004) Aging, immunity and cancer. Curr Opin Immunol 16:151–156
Hamada K, Vannier E, Sacheck JM et al (2005) Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise. FASEB J 19:264–266
Hausser G, Ludewig B, Gelderblom HR et al (1997) Monocyte-derived dendritic cells represent a transient stage of differentiation in the myeloid lineage. Immunobiology 197:534–542
Hayek MG, Mura C, Wu D et al (1997) Enhanced expression of inducible cyclooxygenase with age in murine macrophages. J Immunol 159:2445–2451
Haynes L, Eaton SM, Bums EM et al (2004) Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo. J Immunol 172:5194–5199
Hsu HC, Scott DK, Mountz JD (2005) Impaired apoptosis and immune senescence-cause or effect? Immunol Rev 205:130–146
Iwama H, Ohyashiki JH, Hayashi S et al (1998) Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from narmal individuals. Hum Genet 102:397–402
Iwasa H, Han J, Ishikawa F (2003) Mitogen-activated protein kinase p38 defines the common senescence-signaling pathway. Genes Cells 8:131–144
Janeway CA Jr (2002) Medzhitov R. Innate immune recognition. Annu Rev Immuno1 20:197–216
Jozsi AC, Dupont-Versteegden EE, Taylor-Jones JM et al (2001) Molecular characteristics of aged muscle reflect an altered ability to respond to exercise. Int J Sport Nutr Exerc Metab 11:7–13
Kang Y-S, Kim JY, Bmening SA et al (2004) The C-type lectin SIGN-Rl mediates uptake of the capsular polysaccharide of Streptococcus pneumoniae in the marginal zone of mouse spleen. Proc Natl Acad Sci 101:215–220
Kang KB, Van Der Zypp A, Iannazzo L, Majewski H (2006) Age-related changes in monocyte and platelet cyclooxygenase expression in healthy male humans and rats. Transl Res 2006;148:289–294
Kessel JM, Hayflick J, Weyrich AS et al (1998) Coengagement of ICAM-3 and Fc receptors induces chemokine secretion and spreading by myeloid leucocytes. J Immunol 160:5579–5587
Kiertscher S, Luo J, Dubinett SM, Roth MD (2000) Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells. J Immunol 164:1269–1276
Kohut ML, Senchina DS, Madden KS et al (2004) Age effects on macrophage function vary by tissue site, nature of stimulant, and exercise behavior. Exp Gerontol 39:1347–1360
Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39:687–699
Kurt I, Abasli D, Cihan M et al (2007) Chitotriosidase levels in healthy elderly subjects. Ann N Y Acad Sci 1100:185–188
Lang R, Patel D, Moms JJ, Rutschman RL, Murray PJ (2002) Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol 169:2253–2263
Lavrovsky Y, Chatterjee B, Clark RA, Roy AK (2000) Role of redox-regulated transcription factors in inflammation, aging and age-related diseases. Exp Geronto1 35:521–532
Le Morvan C, Cogne M, Drouet M (2001) HLA-A and HLA-B transcription decrease with ageing in peripheral blood leukocytes. Clin Exp Immunol 125:245–250
Lloberas J, Celada A (2002) Effect of aging on macrophage function. Exp Gerontol 37:1323–1329
Ma J, Chen T, Mandelin J et al (2003) Regulation of macrophage activation. Cell Mol Life Sci 40:2334–2346
Malm C, Sjodin TL, Sjoberg B et al (2004) Leukocytes, cytokines, growth factors and hormones in human skeletal muscle and blood after uphill or downhill running. J Physiol 556:983–1000
Mancuso P, McNish RW, Peters-Golden M, Brock TG (2001) Evaluation of phagocytosis and arachidonate metabolism by alveolar macrophages and recruited neutrophils from F344xBN rats of different ages. Mech Ageing Dev 122:1899–1913
Meydani SN, Han SN, Wu D (2005) Vitamin E and immune response in the aged: molecular mechanisms and clinical implications. Immunol Rev 205:269–284
Mills CD, Kincaid K, Alt JM et al (2000) M-1/M-2 macrophages and the Thl/Th2 paradigm. J Immunol 164:6166–6173
Moffatt OD, Devitt A, Bell ED (1999) Simmons DL, Gregory CD. Macrophage recognition of ICAM-3 on apoptotic leukocytes. J Immunol 162:6800–6810
Monti D, Salvioli S, Capri M et al (2000) Decreased susceptibility to ozidative stress-induced apoptosis of peripheral blood mononuclear cells from healthy elderly and centenarians. Mech Ageing Dev 121:239–250
Montoya MC, Sancho D, Bonello G et al (2002) Role of ICAM-3 in the initial interaction of T lymphocytes and APCs. Nat Immunol 3:159–168
Mosser DM (2003) Thc many faces of macrophage activation. J Leukoc Biol 73:209–212
Njemini R, Lambert M, Demanet C, Mets T (2006) The effect of aging and inflammation on heat shock protein 27 in human monocytes and lymphocytes. Exp Gerontol 41:312–319
Ogawa T, Kitagawa M, Hirokawa K et al (2000) Age-related changes of human bone marrow: a histometric estìmation of proliferative cells, apoptotlc cells, T cells, B cells and macrophages. Mech Ageing Dev 117:57–68
Ortega E, Garcia JJ, De la FM (2000) Modulation of adherence and chemotaxis of macrophages by norepinephrine. Influence of ageing. Mol Cell Biochem 203:113–117
Pascual V, Banchereau J, Palucka AK (2003) The central rote of dendritic cells and interferon- alpha in SLE. Curr Opin Rheumatol 15:548–556
Plackett TP, Boehmer ED, Faunce DE, Kovacs EJ (2004) Aging and innate immune cells. J Leukoc Biol 76:291–299
Pietschmann P, Hahn P, Kudlacek S et al (2000) Surface markers and transendothelial migration of dendritic cells from elderly subjects Exp Gerontol 35:213–224
Plowden J, Renshaw-Hcelscher M, Engleman C et al (2004) Innate immunity in aging: impact on macrophage funclion. Aging Cell 3:161–167
Poynter ME, Daynes RA (1998) Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging. J Biol Chem 273:32833–32841
Przybyla B, Gurley C, Harvey JF et al (2006) Aging alters macrophage properties in human skeletal muscle both at rest and in response to acute resistance exercise. Exp Gerontol 41:329–370
Pulsatelli L, Meliconi R, Mazzetti I et al (2000) Chemokine production by peripheral blood mononuclear cells in elderly subjects. Mech Ageing Dev 20:89–100
Rainer TH, Lam N, Cocks RA (1999) Adrenaline upregulates monocyte L-selectin in vitro. Resuscitation 43:47–55
Rao KMK (2001) MAP kinase activation in macrophages. J Leukoc Biol 69:3–10
Renshaw M, Rockwell J, Engleman C et al (2002) Cutting edge: impaired Toll-like receptor expression and function in aging. J Immuno1 169:4697–4701
Reuben DB, Cheh AL, Harris TB et al (2002) Peripheral blood markers of inflammation predict mortality and functional decline in high-functioning community-dwelling older persons. J Am Geriatr Soc 50:638–644
Ricote M, Valledor AF, Glass CK (2004) Decoding transcriptional programs regulated by PPARs and LXRs in the macrophage: effects on lipid homeostasis, inflammation, and atherosclerosis. Arterioscler Thromb Vasc Bio1 24:230–239
Rossi M, Young JW (2005) Human dendritic cells: potent antigen presenting cells at the crossroads of innate and adaptive immunity. J Immunol 175:1373–1381
Sadeghi HM, Schnelle JF, Thoma JK et al (1999) Phenotypic and functional characteristics of circulating monocytes of elderly persons. Exp Gerontol 34:959–970
Saurwein-Teissl M, Blasko I, Zisterer K et al (2000) An imbalance between pro- and antiinflammatory cytokines, a characteristic feature of old age. Cytokine 12:1160–1161
Sebastian C, Espia M, Serra M et al (2005) MacrophAging: a cellular and molecular review. Immunobiology 210:121–126
Shortman K, Wu L (2004) Are dendritic cells end cells? Nat Immuno1 5:1105–1106
Spencer NF, Norton SI, Harrison LL et al (1996) Dysregulation of IL-10 production with aging: possible linkage to the age-associated decline in DHEA and its sulfated derivative. Exp Gerontol 31:393–408
Spencer NF, Poynter ME, Im SY, Daynes RA (1997) Constitutive activation of NF-kappa B in an animal model of aging. lnt Immuuol 9:1581–1588
Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314
Starr R, Willson TA, Viney EM et al (1997) A family of cytokine-inducible inhibitors of signaling. Nature 387:917–921
Stout RD, Jiang C, Matta B et al (2005) Macrophages sequentially change their functional phenotype in response to changes in micrcenvironmental influences. J Immunol 175:342–349
Stout RD, Suttles J (2005) Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age-associated microenvironmental changes. Immunol Rev 205:60–71
Swift ME, Bums AL, Gray KL, DiPietro LA (2001) Age-related alterations in the inflammatory response to dermal injury. J Invest Dermatol 117:1027–1035
Tracy RP (2003) Emerging relationships of inflammation, cardiovascular disease and chronic diseases of aging. Int J Obes Relat Metab Disord 27:29–34
Uyemura K, Castle SC, Makinodan T (2002) The frail elderly: role of dendritic cells in the susceptibility of infection. Mech Ageing Dev 123:955–962
Visser M, Pahor M, Taaffe DR et al (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the health ABC study. J Gerontol 57:326–332
Walrand S, Guillet C, Boirie Y, Vasson MP (2006) Insulin differentially regulates monocyte and polymorphonuclear neutrophil functions in healthy young and elderly humans. J Clin Endocrinol Metab 91:2738–2748
Weng N (2001) Intetplay between telomere length and telomerase in human leukocyte differentiation and aging. J Leukoc Biol 70:861–867
Williams JC, Fotherby MD, Foster LA et al (2000) Mononuclear cell adhesion to collagen ex vivo is related to pulse pressure in elderly subjects. Atherosclerosis 151:463–469
Wu D, Meydani SN (2004) Mechanism of age-associated upregulation in macrophage PGE2 synthesis. Brain Behav Immun 18:487–494
Wu D, Mura C, Beharka AA et al (1998) Age-associated increase in PGE2 synthesis and COX activity in murine macrophages is reversed by vitamin E. Am J Physiol 275:661–668
Yoon P, Keylock KT, Hartman ME et al (2004) Macrophage hypo-responsiveness to interferon- gamma in aged mice is associated with impaired signaling through Jak-STAT. Mech Ageing Dev 125:137–143
Zhang Y, Blattman JN, Kennedy NJ et al (2004) Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. Nature 430:793–797
Zhang M, Tang H, Guo Z et al (2004) Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol 5:1124–1133
Zissel G, Schlaak M, Muller-Quemheim J (1999) Age-related decrease in accessory cell function of human alveolar macrophages. J Investig Med 47:51.
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Ginaldi, L., De Martinis, M. (2009). Phenotypic and Functional Changes of Circulating Monocytes in Elderly. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_26
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