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Effects of Spaceflight on the Immune System

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Handbook of Space Pharmaceuticals

Abstract

The immune system belongs to the most affected systems during spaceflight, and sensitivity of cells of the human immune system to reduced gravity has been confirmed in numerous studies in real and simulated microgravity. Immune system dysfunction during spaceflight represents a substantial risk for exploration class mission knowledge about the clinical, cellular, and genetic basis of immune system response, and adaptation to altered gravity will provide key information for appropriate risk management, efficient monitoring, and countermeasures against existing limiting factors for human health and performance during manned exploration of the solar system. In spite of the immune system dysregulation, studies indicate an adaptation reaction of the immune system to the new microgravity environment, at least for the T-cell system, starting after 2 weeks and continuing until 6 months or longer, reflected by cytokine concentrations in blood plasma or in stimulation assays. At the cellular level, rapid adaptation responses could be detected as early as after seconds until minutes in T cells and macrophages. Therefore, adaptive responses of cells and the whole organism could be expected under microgravity and altered gravity in general. Preventive countermeasures should therefore consider support and stabilization of the endogenous adaptation programs. Potential countermeasures for risk mitigation are summarized in this chapter. We assume that the immune systems not only have a significant adaptation potential when challenged with low gravitational environments but also provide interesting preventive and therapeutic options for long-term space missions.

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References

  • Adair JE, Kubek SP, Kiem HP (2017) Hematopoietic stem cell approaches to Cancer. Hematol Oncol Clin North Am 31(5):897–912. https://doi.org/10.1016/j.hoc.2017.06.012

    Article  PubMed  Google Scholar 

  • Adrian A, Schoppmann K, Sromicki J et al (2013) The oxidative burst reaction in mammalian cells depends on gravity. Cell Commun Signal 11:98

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arav A, Natan D (2012) Freeze drying of red blood cells: the use of directional freezing and a new radio frequency lyophilization device. Biopreserv Biobank 10(4):386–394. https://doi.org/10.1089/bio.2012.0021

    Article  CAS  PubMed  Google Scholar 

  • Aureli P, Capurso L, Castellazzi AM et al (2011) Probiotics and health: an evidence-based review. Pharmacol Res 63:366–376

    Article  CAS  PubMed  Google Scholar 

  • Aviles H, Belay T, Fountain K et al (2003) Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions. J Appl Physiol 95:491–496

    Article  CAS  PubMed  Google Scholar 

  • Aviles H, Belay T, Vance M et al (2004) Active hexose correlated compound enhances the immune function of mice in the hindlimb-unloading model of spaceflight conditions. J Appl Physiol 97:1437–1444

    Article  CAS  PubMed  Google Scholar 

  • Bassetti S, Bischoff WE, Walter M et al (2005) Dispersal of Staphylococcus aureus into the air associated with a rhinovirus infection. Infect Control Hosp Epidemiol 26:196–203

    Article  PubMed  Google Scholar 

  • Battista N, Meloni MA, Bari M et al (2012) 5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: data from the ROALD experiment. FASEB J 26:1791–1798

    Article  CAS  PubMed  Google Scholar 

  • Bechler B, Cogoli A, Cogoli-Greuter M et al (1992) Activation of microcarrier-attached lymphocytes in microgravity. Biotechnol Bioeng 40:991–996

    Article  CAS  PubMed  Google Scholar 

  • Bhatia R, Van Heijzen K, Palmer A, Komiya A, Slovak ML, Chang KL, Fung H, Krishnan A, Molina A, Nademanee A, O’Donnell M, Popplewell L, Rodriguez R, Forman SJ, Bhatia S (2005) Longitudinal assessment of hematopoietic abnormalities after autologous hematopoietic cell transplantation for lymphoma. J Clin Oncol 23(27):6699–6711. https://doi.org/10.1200/JCO.2005.10.330

    Article  PubMed  Google Scholar 

  • Blaber E, Marçal H, Burns BP (2010) Bioastronautics: the influence of microgravity on astronaut health. Astrobiology 10:463–473

    Article  PubMed  Google Scholar 

  • Birmele MCJ, Newsham G, Roberts M (2011) Antimicrobial materials for advanced microbial control in spacecraft water systems. AIAA technical paper 5276

    Google Scholar 

  • Boonyaratanakornkit JB, Cogoli A, Li CF et al (2005) Key gravity-sensitive signaling pathways drive T cell activation. FASEB J 19:2020–2022

    Article  CAS  PubMed  Google Scholar 

  • Borchers AT, Keen CL, Gershwin ME (2002) Microgravity and immune responsiveness. Nutrition 18:889–898

    Article  PubMed  Google Scholar 

  • Boxio R (2004) Effects of a long-term spaceflight on immunoglobulin heavy chains of the urodele amphibian Pleurodeles waltl. J Appl Physiol 98:905–910

    Article  PubMed  CAS  Google Scholar 

  • Brungs S, Kolanus W, Hemmersbach R (2015) Syk phosphorylation – a gravisensitive step in macrophage signalling. Cell Commun Signal 13:9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Buchanan SS, Menze MA, Hand SC, Pyatt DW, Carpenter JF (2005) Cryopreservation of human hematopoietic stem and progenitor cells loaded with trehalose: transient permeabilization via the adenosine triphosphate-dependent P2Z receptor channel. Cell Preserv Technol 3(4):212–222. https://doi.org/10.1089/cpt.2005.3.212

    Article  CAS  Google Scholar 

  • Buchanan SS, Pyatt DW, Carpenter JF (2010) Preservation of differentiation and clonogenic potential of human hematopoietic stem and progenitor cells during lyophilization and ambient storage. PLoS One 5(9):e12518. https://doi.org/10.1371/journal.pone.0012518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burman J, Tolf A, Hagglund H, Askmark H (2018) Autologous haematopoietic stem cell transplantation for neurological diseases. J Neurol Neurosurg Psychiatry 89(2):147–155. https://doi.org/10.1136/jnnp-2017-316271

    Article  PubMed  Google Scholar 

  • Chang TT, Spurlock SM, Candelario TLT et al (2015) Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines. FASEB J 29:4122–4132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang TT, Walther I, Li CF et al (2012) The Rel/NF-B pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity. J Leuk Biol 92:1133–1145

    Article  CAS  Google Scholar 

  • Chapes SK, Simske SJ, Sonnenfeld G et al (1999) Effects of spaceflight and PEG-IL-2 on rat physiological and immunological responses. J Appl Physiol 86:2065–2076

    Article  CAS  PubMed  Google Scholar 

  • Choukèr A, Ullrich O (2016) The immune system in space: are we prepared? Springer International Publishing, pp 123–127

    Google Scholar 

  • Clauß-Lendzian E, Vaishampayan A, Kok J et al (2015) Einsatz von neuen antimikrobiellen Oberflächenbeschichtungen auf der ISS. Tagungsband Nationales Symposium Forschung unter Weltraumbedingungen, pp 41

    Google Scholar 

  • Clauß-Lendzian E, Vaishampayan A, Kok J et al (2018) Stress response of a clinical enterococcus faecalis isolate subjected to a novel antimicrobial surface coating. Microbiol Res 207:53–64

    Article  PubMed  CAS  Google Scholar 

  • Clegg JS (1965) The origin of trehalose and its significance during the formation of encysted dormant embryos of Artemia salina. Comp Biochem Physiol 14:135–143

    Article  CAS  PubMed  Google Scholar 

  • Clegg JS (2001) Cryptobiosis – a peculiar state of biological organization. Comp Biochem Physiol B Biochem Mol Biol 128(4):613–624

    Article  CAS  PubMed  Google Scholar 

  • Clément G (2011) Fundamentals of space medicine, Space Technology Library, 2nd edn. Springer, pp 273–279

    Google Scholar 

  • Cogoli A (1996) Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies. J Gravit Physiol 3:1–9

    CAS  PubMed  Google Scholar 

  • Cogoli A, Bechler B, Cogoli-Greuter M et al (1993) Mitogenic signal transduction in T lymphocytes in microgravity. J Leuk Biol 53:569–575

    Article  CAS  Google Scholar 

  • Cogoli A, Bechler B, Müller O et al (1987) Effect of microgravity on lymphocyte activation. In: Norderney symposium on scientific results of the German Spacelab Mission D 1, Norderney, Federal Republic of Germany, pp 366–375

    Google Scholar 

  • Cogoli A, Cogoli-Greuter M (1997) Activation and proliferation of lymphocytes and other mammalian cells in microgravity. In: Advances in space biology and medicine. Elsevier BV, pp 33–79

    Google Scholar 

  • Cogoli A, Tschopp A (1985) Lymphocyte reactivity during spaceflight. Immunol Today 6:1–4

    Article  CAS  PubMed  Google Scholar 

  • Cogoli A, Tschopp A, Fuchs-Bislin P (1984) Cell sensitivity to gravity. Science 225:228–230

    Article  CAS  PubMed  Google Scholar 

  • Cohrs RJ, Mehta SK, Schmid DS et al (2008) Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts. J Med Virol 80:1116–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Comet B (2001) Limiting factors for human health and performance: microgravity and reduced gravity. HUMEX-TN-002 study on the survivability and adaptation of humans to long-duration interplanetary and planetary environments. Technical note 2: critical assessments of the limiting factors for human health and performance and recommendation of countermeasures

    Google Scholar 

  • Crabbé A, Schurr MJ, Monsieurs P et al (2011) Transcriptional and proteomic responses of Pseudomonas aeruginosa PAO1 to spaceflight conditions involve Hfq regulation and reveal a role for oxygen. Appl Environ Microbiol 77:1221–1230

    Article  PubMed  CAS  Google Scholar 

  • Crowe JH, Crowe LM, Chapman D (1984) Preservation of membranes in anhydrobiotic organisms: the role of trehalose. Science 223(4637):701–703. https://doi.org/10.1126/science.223.4637.701

    Article  CAS  PubMed  Google Scholar 

  • Crowe JH, Hoekstra FA, Crowe LM (1992) Anhydrobiosis. Annu Rev Physiol 54:579–599. https://doi.org/10.1146/annurev.ph.54.030192.003051

    Article  CAS  PubMed  Google Scholar 

  • Crucian B (2015) Countermeasure options for immune system dysregulation. Exobiology; Aerospace Medicine: NASA

    Google Scholar 

  • Crucian B, Babiak-Vazquez A, Johnston S et al (2016a) Incidence of clinical symptoms during long-duration orbital spaceflight. Int J Gen Med 9:383–391

    Article  PubMed  PubMed Central  Google Scholar 

  • Crucian BE, Cubbage ML, Sams CF (2000) Altered cytokine production by specific human peripheral blood cell subsets immediately following space flight. J Interf Cytokine Res 20:547–556

    Article  CAS  Google Scholar 

  • Crucian B, Johnston S, Mehta S et al (2016b) A case of persistent skin rash and rhinitis with immune system dysregulation onboard the International Space Station. J Allergy Clin Immunol Pract 4:759–762

    Article  PubMed  Google Scholar 

  • Crucian B, Stowe R, Mehta S et al (2012) Immune system dysregulation occurs during short duration spaceflight on board the space shuttle. J Clin Immunol 33:456–465

    Article  PubMed  CAS  Google Scholar 

  • Crucian B, Stowe RP, Mehta S (2015) Alterations in adaptive immunity persist during long-duration spaceflight. NPJ Microgravity 1:15013

    Article  PubMed  PubMed Central  Google Scholar 

  • Crucian BE, Stowe RP, Pierson DL et al (2008) Immune system dysregulation following short- vs long-duration spaceflight. Aviat Space Environ Med 79:835–843

    Article  PubMed  Google Scholar 

  • Cubano LA, Lewis ML (2000) Fas/APO-1 protein is increased in spaceflown lymphocytes (Jurkat). Exp Gerontol 35:389–400

    Article  CAS  PubMed  Google Scholar 

  • Cubano L, Maldonado H (2005) Immune cells under altered gravity conditions. Bol Asoc Med P R 98:223–228

    Google Scholar 

  • Damon LE, Damon LE (2009) Mobilization of hematopoietic stem cells into the peripheral blood. Expert Rev Hematol 2(6):717–733. https://doi.org/10.1586/ehm.09.54

    Article  CAS  PubMed  Google Scholar 

  • Dubinin N, Vaulina E (1976) The evolutionary role of gravity. Life Sci Space Res 14:47–55

    CAS  PubMed  Google Scholar 

  • Eroglu A, Russo MJ, Bieganski R, Fowler A, Cheley S, Bayley H, Toner M (2000) Intracellular trehalose improves the survival of cryopreserved mammalian cells. Nat Biotechnol 18(2):163–167. https://doi.org/10.1038/72608

    Article  CAS  PubMed  Google Scholar 

  • Frippiat JP (2013) Contribution of the urodele amphibian Pleurodeles waltl to the analysis of spaceflight-associated immune system deregulation. Mol Immunol 56:434–441

    Article  CAS  PubMed  Google Scholar 

  • Frippiat JP, Crucian BE, De Quervain DJ et al (2016) Towards human exploration of space: the THESEUS review series on immunology research priorities. NPJ Microgravity 2:16040

    Article  PubMed  PubMed Central  Google Scholar 

  • Fuchs BB, Medvedev AE (1993) Countermeasures for ameliorating in-flight immune dysfunction. J Leuk Biol 54:245–252

    Article  CAS  Google Scholar 

  • Green RD, Agui JH, Vijayakumar R et al (2017) Filter efficiency and pressure testing of returned ISS bacterial filter elements after 2.5 years of continuous operation. International conference on environmental systems (ICES 2016), GRC-E-DAA-TN30499

    Google Scholar 

  • Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T (1999) Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci U S A 96(12):6879–6884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gridley DS, Mao XW, Stodieck LS et al (2013) Changes in mouse thymus and spleen after return from the STS-135 mission in space. PLoS One 8(9):e75097. https://doi.org/10.1371/journal.pone.0075097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grove DS, Pishak SA, Mastro AM (1995) The effect of a 10-day space flight on the function, phenotype, and adhesion molecule expression of splenocytes and lymph node lymphocytes. Exp Cell Res 219:102–109

    Article  CAS  PubMed  Google Scholar 

  • Gu JD, Roman M, Esselman T et al (1998) The role of microbial biofilms in deterioration of space station candidate materials. Int Biodeter Biodegr 41(1):25–33

    Article  CAS  Google Scholar 

  • Guo N, Puhlev I, Brown DR, Mansbridge J, Levine F (2000) Trehalose expression confers desiccation tolerance on human cells. Nat Biotechnol 18(2):168–171. https://doi.org/10.1038/72616

    Article  CAS  PubMed  Google Scholar 

  • Gueguinou N, Huin-Schohn C, Bascove M et al (2009) Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth’s orbit? J Leuk Biol 86:1027–1038

    Article  CAS  Google Scholar 

  • Guridi A, Diederich AK, Aguila-Arcos S et al (2015) New antimicrobial contact catalyst killing antibiotic resistant clinical and waterborne pathogens. Mater Sci Eng C Mater Biol Appl 50:1–11. https://doi.org/10.1016/j.msec.2015.01.080

    Article  CAS  PubMed  Google Scholar 

  • Hadzantonis M, O'Neill H (1999) Review: dendritic cell immunotherapy for melanoma. Cancer Biother Radiopharm 14(1):11–22

    Article  CAS  PubMed  Google Scholar 

  • Hahn C, Hans M, Hein C et al (2017) Pure and oxidized copper materials as potential antimicrobial surfaces for spaceflight activities. Astrobiology 17(12):1183–1191

    Article  CAS  PubMed  Google Scholar 

  • Hawkins WR, Zieglschmid JF (1975) Clinical aspects of crew health. In: Biomedical results of Apollo: NASA

    Google Scholar 

  • Holovati JL, Hannon JL, Gyongyossy-Issa MI, Acker JP (2009) Blood preservation workshop: new and emerging trends in research and clinical practice. Transfus Med Rev 23(1):25–41. https://doi.org/10.1016/j.tmrv.2008.09.003

    Article  PubMed  Google Scholar 

  • Horneck G, Klaus DM, Mancinelli RL (2010) Space microbiology. Microbiol Mol Biol Rev 74(1):121–156. https://doi.org/10.1128/MMBR.00016-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes-Fulford M, Chang T, Li CF (2008) Effect of gravity on monocyte differentiation. In: 10th ESA life sciences symposium/29th annual ISGP meeting/24th annual ASGSB meeting/ELGRA symposium “life in space for life on earth, 22–27 June 2008

    Google Scholar 

  • Hughes-Fulford M, Chang TT, Martinez EM et al (2015) Spaceflight alters expression of microRNA during T-cell activation. FASEB J 29:4893–4900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ilyin V (2005) Microbiological status of cosmonauts during orbital spaceflights on Salyut and Mir orbital stations. Acta Astronaut 56:839–850

    Article  CAS  PubMed  Google Scholar 

  • Ingber DE (1999) How cells (might) sense microgravity. FASEB J 13:S3–S15

    Article  CAS  PubMed  Google Scholar 

  • Juergensmeyer MA, Juergensmeyer EA, Guikema JA (1999) Long-term exposure to spaceflight conditions affects bacterial response to antibiotics. Microgravity Sci Technol 12(1):41–47

    CAS  PubMed  Google Scholar 

  • Karimi M, Cao TM, Baker JA, Verneris MR, Soares L, Negrin RS (2005) Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells. J Immunol 175(12):7819–7828

    Article  CAS  PubMed  Google Scholar 

  • Kennedy A, Guan J, Ware J (2007) Countermeasures against space radiation induced oxidative stress in mice. Radiat Environ Biophys 46:201–203

    Article  CAS  PubMed  Google Scholar 

  • Kennedy AR, Ware JH, Guan J et al (2004) Selenomethionine protects against adverse biological effects induced by space radiation. Free Radic Biol Med 36:259–266

    Article  CAS  PubMed  Google Scholar 

  • Kheirolomoom A, Satpathy GR, Torok Z, Banerjee M, Bali R, Novaes RC, Little E, Manning DM, Dwyre DM, Tablin F, Crowe JH, Tsvetkova NM (2005) Phospholipid vesicles increase the survival of freeze-dried human red blood cells. Cryobiology 51(3):290–305. https://doi.org/10.1016/j.cryobiol.2005.08.003

    Article  CAS  PubMed  Google Scholar 

  • Khodadad C, Oubre C, Castro V et al (2017) A PCR based microbial monitoring alternative method of detection and identification of microbes aboard ISS. https://ntrs.nasa.gov/search.jsp?R=20170002604. 2018-03-21T16:02:57+00:00Z

  • Kimzey SL, Fischer CL, Johnson PC et al (1975) Hematology and immunology studies. In: Biomedical results from Skylab, 1st edn. NASA

    Google Scholar 

  • Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, Shizuru JA, Weissman IL (2003) Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol 21:759–806. https://doi.org/10.1146/annurev.immunol.21.120601.141007

    Article  CAS  PubMed  Google Scholar 

  • Konstantinova IV, Rykova M, Lesnyak AT et al (1993) Immune changes during long-duration missions. J Leuk Biol 54:189–201

    Article  CAS  Google Scholar 

  • Kulkarni A, Yamauchi K, Hales N et al (2002) Nutrition beyond nutrition: plausibility of immunotrophic nutrition for space travel. Clin Nutr 21:231–238

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni A, Yamauchi K, Sundaresan A et al (2007) Countermeasure for space flight effects on immune system: nutritional nucleotides. Gravit Space Biol Bull 18:101–102

    Google Scholar 

  • Lebsack TW, Fa V, Woods C et al (2010) Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors. J Cell Biochem 110:372–381

    CAS  PubMed  Google Scholar 

  • Lewis ML, Reynolds JL, Cubano LA et al (1998) Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J 12:1007–1018

    Article  CAS  PubMed  Google Scholar 

  • Lewis ML, Cubano LA, Zhao B et al (2001) cDNA microarray reveals altered cytoskeletal gene expression in space-flown leukemic T lymphocytes (Jurkat). FASEB J 15:1783–1785

    Article  CAS  PubMed  Google Scholar 

  • Leys NM, Hendrickx L, De Boever P et al (2004) Space flight effects on bacterial physiology. J Biol Regul Homeost Agents 18(2):193–199

    CAS  PubMed  Google Scholar 

  • Lichter JA, Van Vliet KJ, Rubner MF (2009) Design of antibacterial surfaces and interfaces: polyelectrolyte multilayers as a multifunctional platform. Macromolecules 42:8573–8586

    Article  CAS  Google Scholar 

  • Limouse M, Manié S, Konstantinova I et al (1991) Inhibition of phorbol ester-induced cell activation in microgravity. Exp Cell Res 197:82–86

    Article  CAS  PubMed  Google Scholar 

  • Lynch S, Mukundakrishnan K, Benoit M et al (2006) Escherichia coli biofilms formed under low-shear modeled microgravity in a ground-based system. Appl Environ Microbiol 72:7701–7710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mah TF, O’Toole GA (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9(1):34–39

    Article  CAS  PubMed  Google Scholar 

  • Makimura K, Satoh K, Sugita T et al (2011) Fungal biota in manned space environment and impact on human health. Jpn J Hyg 66(1):77–82

    Article  Google Scholar 

  • Makino S, Ikegami S, Kano H et al (2006) Immunomodulatory effects of polysaccharides produced by Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1. J Dairy Sci 89:2873–2881

    Article  CAS  PubMed  Google Scholar 

  • Mangala LS, Zhang Y, He Z et al (2011) Effects of simulated microgravity on expression profile of MicroRNA in human lymphoblastoid cells. J Biol Chem 286:32483–32490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martineau AR, Timms PM, Bothamley GH et al (2011) High-dose vitamin D 3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 377:242–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mata-Molanes JJ, Sureda Gonzalez M, Valenzuela Jimenez B, Martinez Navarro EM, Brugarolas Masllorens A (2017) Cancer immunotherapy with cytokine-induced killer cells. Target Oncol 12(3):289–299. https://doi.org/10.1007/s11523-017-0489-2

    Article  PubMed  Google Scholar 

  • Mehta SK, Cohrs RJ, Forghani B et al (2003) Stress-induced subclinical reactivation of varicella zoster virus in astronauts. J Med Virol 72:174–179

    Article  Google Scholar 

  • Mehta SK, Crucian BE, Stowe RP et al (2013) Reactivation of latent viruses is associated with increased plasma cytokines in astronauts. Cytokine 61:205–209

    Article  CAS  PubMed  Google Scholar 

  • Mehta SK, Stowe RP, Feiveson AH et al (2000) Reactivation and shedding of cytomegalovirus in astronauts during spaceflight. J Infect Dis 182:1761–1764

    Article  CAS  PubMed  Google Scholar 

  • Mermel LA (2013) Infection prevention and control during prolonged human space travel. Clin Infect Dis 56:123–130

    Article  PubMed  Google Scholar 

  • Mills PJ, Meck JV, Waters WW et al (2001) Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of Mission duration. Psychosom Med 63:886–890

    Article  CAS  PubMed  Google Scholar 

  • Moore D, Bie P, Oser H (eds) (2012) Biological and medical research in space: an overview of life sciences research in microgravity, 1st edn. Springer Science and Business Media

    Google Scholar 

  • Morey-Holton ER (2003) The impact of gravity on life. In: Rothschild L, Lister A (eds) Evolution on planet earth: the impact of the physical environment. Academic, New York, pp 143–159

    Chapter  Google Scholar 

  • Nademanee A, Sniecinski I, Schmidt GM, Dagis AC, O’Donnell MR, Snyder DS, Parker PM, Stein AS, Smith EP, Molina A et al (1994) High-dose therapy followed by autologous peripheral-blood stem-cell transplantation for patients with Hodgkin’s disease and non-Hodgkin’s lymphoma using unprimed and granulocyte colony-stimulating factor-mobilized peripheral-blood stem cells. J Clin Oncol 12(10):2176–2186

    Article  CAS  PubMed  Google Scholar 

  • NAS (2001) The National Academies of Science, Engineering and Medicine. Recapturing a future for space exploration: life and physical sciences research for a new era. The National Academic Press, Washington, DC

    Google Scholar 

  • NASA Office of Inspector General (2015) NASA’s efforts to manage health and human performance risks for space exploration. Report no. IG-16-003

    Google Scholar 

  • Nickerson CA, Ott CM, Wilson JW et al (2004) Microbial responses to microgravity and other low-shear environments. Microbiol Mol Biol Rev 68:345–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Novikova N (2004) Review of the knowledge of microbial contamination of the Russian manned spacecraft. Microb Ecol 47(2):127–132. https://doi.org/10.1007/s00248-003-1055-2

    Article  CAS  PubMed  Google Scholar 

  • Novikova N, De Boever P, Poddubko S et al (2006) Survey of environmental biocontamination on board the international Space Station. Res Microbiol 157(1):5–12. https://doi.org/10.1016/j.resmic.2005.07.010

    Article  PubMed  Google Scholar 

  • Oliver AE (2012) Dry state preservation of nucleated cells: progress and challenges. Biopreserv Biobank 10(4):376–385. https://doi.org/10.1089/bio.2012.0020

    Article  CAS  PubMed  Google Scholar 

  • Oliver AE, Jamil K, Crowe JH, Tablin F (2004) Loading human mesenchymal stem cells with trehalose by fluid-phase endocytosis. Cell Preser Technol 2(1):35–49. https://doi.org/10.1089/153834404322708745

    Article  CAS  Google Scholar 

  • Ott CM, Bruce RJ, Pierson DL (2004) Microbial characterization of free floating condensate aboard the Mir space station. Microb Ecol 47(2):133–136. https://doi.org/10.1007/s00248-003-1038-3

    Article  CAS  PubMed  Google Scholar 

  • Paulsen K, Thiel C, Timm J et al (2010) Microgravity-induced alterations in signal transduction in cells of the immune system. Acta Astronaut 67:1116–1125

    Article  CAS  Google Scholar 

  • Pellis NR, Goodwin TJ, Risin D et al (1997) Changes in gravity inhibit lymphocyte locomotion through type I collagen. In Vitro Cell Dev Biol Anim 33:398–405

    Article  CAS  PubMed  Google Scholar 

  • Pende D, Rivera P, Marcenaro S, Chang CC, Biassoni R, Conte R, Kubin M, Cosman D, Ferrone S, Moretta L, Moretta A (2002) Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res 62(21):6178–6186

    CAS  PubMed  Google Scholar 

  • Pierson DL (2001) Microbial contamination of spacecraft. Gravit Space Biol Bull 14(2):1–6

    CAS  PubMed  Google Scholar 

  • Pierson DL, Stowe RP, Phillips TM et al (2005) Epstein–Barr virus shedding by astronauts during space flight. Brain Behav Immun 19:235–242

    Article  CAS  PubMed  Google Scholar 

  • Read MS, Reddick RL, Bode AP, Bellinger DA, Nichols TC, Taylor K, Smith SV, McMahon DK, Griggs TR, Brinkhous KM (1995) Preservation of hemostatic and structural properties of rehydrated lyophilized platelets: potential for long-term storage of dried platelets for transfusion. Proc Natl Acad Sci U S A 92(2):397–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenzweig JA, Abogunde O, Thomas K et al (2010) Spaceflight and modeled microgravity effects on microbial growth and virulence. Appl Microbiol Biotechnol 85:885–891

    Article  CAS  PubMed  Google Scholar 

  • Ryan MA, Zhou H, Buehler MG et al (2004) Monitoring space shuttle air quality using the jet Propulsion Laboratory electronic nose. IEEE Sensors J 4(3):337–347

    Article  CAS  Google Scholar 

  • Rykova MP, Antropova EN, Larina IM et al (2008) Humoral and cellular immunity in cosmonauts after the ISS missions. Acta Astronaut 63:697–705

    Article  Google Scholar 

  • Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee HG, Steinle A (2003) Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood 102(4):1389–1396. https://doi.org/10.1182/blood-2003-01-0019

    Article  CAS  PubMed  Google Scholar 

  • Sangiolo D, Martinuzzi E, Todorovic M, Vitaggio K, Vallario A, Jordaney N, Carnevale-Schianca F, Capaldi A, Geuna M, Casorzo L, Nash RA, Aglietta M, Cignetti A (2008) Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers. Int Immunol 20(7):841–848. https://doi.org/10.1093/intimm/dxn042

    Article  CAS  PubMed  Google Scholar 

  • Satpathy GR, Torok Z, Bali R, Dwyre DM, Little E, Walker NJ, Tablin F, Crowe JH, Tsvetkova NM (2004) Loading red blood cells with trehalose: a step towards biostabilization. Cryobiology 49(2):123–136. https://doi.org/10.1016/j.cryobiol.2004.06.001

    Article  CAS  PubMed  Google Scholar 

  • Schmidt-Wolf IG, Lefterova P, Mehta BA, Fernandez LP, Huhn D, Blume KG, Weissman IL, Negrin RS (1993) Phenotypic characterization and identification of effector cells involved in tumor cell recognition of cytokine-induced killer cells. Exp Hematol 21(13):1673–1679

    CAS  PubMed  Google Scholar 

  • Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG, Weissman IL (1991) Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. J Exp Med 174(1):139–149

    Article  CAS  PubMed  Google Scholar 

  • Schmitt DA, Hatton JP, Emond C et al (1996) The distribution of protein kinase C in human leukocytes is altered in microgravity. FASEB J 10:1627–1634

    Article  CAS  PubMed  Google Scholar 

  • Schwarzenberg M, Pippia P, Meloni MA et al (1999) Signal transduction in T lymphocytes – a comparison of the data from space, the free fall machine and the random positioning machine. Adv Space Res 24:793–800

    Article  CAS  PubMed  Google Scholar 

  • Shearer WT, Ochs HD, Lee BN et al (2009) Immune responses in adult female volunteers during the bed-rest model of spaceflight: antibodies and cytokines. J Allergy Clin Immunol 123:900–905

    Article  CAS  PubMed  Google Scholar 

  • Singh KP, Kumari R, DuMond JW (2010) Simulated microgravity-induced epigenetic changes in human lymphocytes. J Cell Biochem 111:123–129

    Article  CAS  PubMed  Google Scholar 

  • Smith SM, Zwart SR (2008) Nutrition issues for space exploration. Acta Astronaut 63:609–613

    Article  Google Scholar 

  • Sonnenfeld G (1999) Space flight, microgravity, stress, and immune responses. Adv Space Res 23:1945–1953

    Article  CAS  PubMed  Google Scholar 

  • Sonnenfeld G (2002) The immune system in space and microgravity. Med Sci Sports Exerc 34:2021–2027

    Article  CAS  PubMed  Google Scholar 

  • Sonnenfeld G (2005) The immune system in space, including earth-based benefits of space-based research. Curr Pharm Biotechnol 6:343–349

    Article  CAS  PubMed  Google Scholar 

  • Sonnenfeld G, Butel JS, Shearer WT (2003) Effects of the space flight environment on the immune system. Rev Environ Health 18:1–18

    Article  PubMed  Google Scholar 

  • Sonnenfeld G, Shearer WT (2002) Immune function during space flight. Nutrition 18:899–903

    Article  CAS  PubMed  Google Scholar 

  • Shirakashi R, Kostner CM, Muller KJ, Kurschner M, Zimmermann U, Sukhorukov VL (2002) Intracellular delivery of trehalose into mammalian cells by electropermeabilization. J Membr Biol 189(1):45–54. https://doi.org/10.1007/s00232-002-1003-y

    Article  CAS  PubMed  Google Scholar 

  • Stein T, Leskiw M (2000) Oxidant damage during and after spaceflight. Am J Physiol Endocrinol Metab 278:E375–E382

    Article  CAS  PubMed  Google Scholar 

  • Stowe RP, Pierson DL, Feeback DL et al (2000) Stress-induced reactivation of Epstein-Barr virus in astronauts. Neuroimmunomodulation 8:51–58

    Article  CAS  PubMed  Google Scholar 

  • Stowe RP, Sams CF, Mehta SK et al (1999) Leukocyte subsets and neutrophil function after short-term spaceflight. J Leuk Biol 65:179–186

    Article  CAS  Google Scholar 

  • Stowe RP, Sams CF, Pierson DL (2003) Effects of mission duration on neuroimmune responses in astronauts. Aviat Space Environ Med 74:1281–1284

    PubMed  Google Scholar 

  • Su L, Chang D, Liu C (2013) The development of space microbiology in the future: the value and significance of space microbiology research. Future Microbiol 8(1):5–8. https://doi.org/10.2217/fmb.12.127

    Article  CAS  PubMed  Google Scholar 

  • Sundaresan A, Risin D, Pellis NR (2002) Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity. In Vitro Cell Dev Biol Anim 38:118

    Article  PubMed  Google Scholar 

  • Tauber S, Hauschild S, Crescio C et al (2013) Signal transduction in primary human T lymphocytes in altered gravity – results of the MASER-12 suborbital space flight mission. Cell Commun Signal 11:32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tauber S, Hauschild S, Paulsen K et al (2015) Signal transduction in primary human T lymphocytes in altered gravity during parabolic flight and clinostat experiments. Cell Physiol Biochem 35:1034–1051

    Article  CAS  PubMed  Google Scholar 

  • Tauber S, Lauber B, Paulsen K et al (2017) Cytoskeletal stability and metabolic alterations in primary human macrophages in long-term microgravity. PLoS One 12:e0175599. https://doi.org/10.1371/journal.pone.0175599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor GR (1993) Immune changes during short-duration missions. J Leuk Biol 54:202–208

    Article  CAS  Google Scholar 

  • Taylor PW, Sommer AP (2005) Towards rational treatment of bacterial infections during extended space travel. Int J Antimicrob Agents 26(3):183–187. https://doi.org/10.1016/j.ijantimicag.2005.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thiel CS, Paulsen K, Bradacs G et al (2012) Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity. Cell Commun Signal 10:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thiel CS, Lauber BA, Polzer J et al (2017a) Time course of cellular and molecular regulation in the immune system in altered gravity: progressive damage or adaptation? REACH – Rev Hum Space Exploration 5:22–32

    Google Scholar 

  • Thiel CS, de Zélicourt D, Tauber S et al (2017b) Rapid adaptation to microgravity in mammalian macrophage cells. Sci Rep 7:43

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thiel CS, Hauschild S, Huge A et al (2017c) Dynamic gene expression response to altered gravity in human T cells. Sci Rep 7:5204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thiel CS, Huge A, Hauschild S et al (2017d) Stability of gene expression in human T cells in different gravity environments is clustered in chromosomal region 11p15. 4. NPJ Microgravity 3:22

    Article  PubMed  PubMed Central  Google Scholar 

  • Thornhill SG, Kumar M (2018) Biological filters and their use in potable water filtration systems in spaceflight conditions. Life Sci Space Res 17:40–43

    Article  Google Scholar 

  • Török Z, Satpathy GR, Banerjee M et al (2005) Preservation of trehalose-loaded red blood cells by lyophilization. Cell Preserv Technol 3(2):96–111. https://doi.org/10.1089/cpt.2005.3.96

    Article  Google Scholar 

  • Van Houdt R, Mijnendonckx K, Leys N (2012) Microbial contamination monitoring and control during human space missions. Planet Space Sci 60(1):115–120. https://doi.org/10.1016/j.pss.2011.09.001

    Article  Google Scholar 

  • Verneris MR, Karimi M, Baker J, Jayaswal A, Negrin RS (2004) Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells. Blood 103(8):3065–3072. https://doi.org/10.1182/blood-2003-06-2125

    Article  CAS  PubMed  Google Scholar 

  • Vidyasekar P, Shyamsunder P, Arun R et al (2015) Genome wide expression profiling of cancer cell lines cultured in microgravity reveals significant dysregulation of cell cycle and microRNA gene networks. PLoS One 10:e0135958

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Viktorov AN, Novikova ND, Deshevaia EA (1992) The cabin microflora of manned space vehicles and the problem of the biological destruction of the construction materials used in them. Aerosp Environ Med 26(3):41–48

    CAS  Google Scholar 

  • Voermans C, van Hennik PB, van der Schoot CE (2001) Homing of human hematopoietic stem and progenitor cells: new insights, new challenges? J Hematother Stem Cell Res 10(6):725–738. https://doi.org/10.1089/152581601317210827

    Article  CAS  PubMed  Google Scholar 

  • Volkmann D, Baluska F (2006) Gravity: one of the driving forces for evolution. Protoplasma 229:143–148

    Article  CAS  PubMed  Google Scholar 

  • Vorselen D, Roos WH, Mackintosh FC et al (2014) The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells. FASEB J 28:536–547

    Article  CAS  PubMed  Google Scholar 

  • Voss E (1984) Prolonged weightlessness and humoral immunity. Science 225:214–215

    Article  PubMed  Google Scholar 

  • Wan XS, Bloch P, Ware JH et al (2005) Detection of oxidative stress induced by low-and high-linear energy transfer radiation in cultured human epithelial cells. Radiat Res 163:364–368

    Article  CAS  PubMed  Google Scholar 

  • Wan XS, Ware JH, Zhou Z et al (2006) Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents. Int J Radiat Oncol Biol Phys 64:1475–1481

    Article  CAS  PubMed  Google Scholar 

  • Ward NE, Pellis NR, Risin SA et al (2006) Gene expression alterations in activated human T-cells induced by modeled microgravity. J Cell Biochem 99:1187–1202

    Article  CAS  PubMed  Google Scholar 

  • Ward C, Rettig TA, Hlavacek S et al (2018) Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice. Life Sci Space Res 16:63–75. https://doi.org/10.1016/j.lssr.2017.11.003

    Article  Google Scholar 

  • Weber TP, Stilianakis NI (2008) Inactivation of influenza A viruses in the environment and modes of transmission: a critical review. J Infect 57:361–373

    Article  PubMed  PubMed Central  Google Scholar 

  • White RJ, Averner M (2001) Humans in space. Nature 409:1115–1118

    Article  CAS  PubMed  Google Scholar 

  • Williams D, Kuipers A, Mukai C et al (2009) Acclimation during space flight: effects on human physiology. Can Med Assoc J 180:1317–1323

    Article  Google Scholar 

  • Wilson J, Ott C, Zu Bentrup KH et al (2007) Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq. Proc Natl Acad Sci 104:16299–16304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolkers WF, Walker NJ, Tablin F et al (2001) Human platelets loaded with trehalose survive freeze-drying. Cryobiology 42(2):79–87. https://doi.org/10.1006/cryo.2001.2306

    Article  CAS  PubMed  Google Scholar 

  • Wolkers WF, Walker NJ, Tamari Y et al (2002) Towards a clinical application of freeze-dried human platelets. Cell Preserv Technol 1(3):175–188. https://doi.org/10.1089/153834402765035617

    Article  Google Scholar 

  • Zanello SB, Tadigotla V, Hurley J et al (2018) Inflammatory gene expression signatures in idiopathic intracranial hypertension: possible implications in microgravity-induced ICP elevation. NPJ Microgravity 4:1. https://doi.org/10.1038/s41526-017-0036-6

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Glesne D, Huberman E (2003) A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc Natl Acad Sci U S A 100(5):2426–2431. https://doi.org/10.1073/pnas.0536882100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zvaifler NJ, Marinova-Mutafchieva L et al (2000) Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2(6):477–488. https://doi.org/10.1186/ar130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zwart SR, Mehta SK, Ploutz-Snyder R et al (2011) Response to vitamin D supplementation during Antarctic winter is related to BMI, and supplementation can mitigate Epstein-Barr virus reactivation. J Nutr 141:692–697

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This chapter is partially based on and adapted from Thiel CS, Lauber BA, Polzer J, Ullrich O (2017). Time course of cellular and molecular regulation in the immune system in altered gravity: Progressive damage or adaptation? REACH-Reviews in Human Space Exploration 5: 22-23 under the Creative Commons Attribution (CC BY) and from Chouker A and Ullrich O (eds.), The Immune System in Space: Are we prepared? Springer Briefs, 2017, chapter 7 and 8 (authors: Lauber B, Layer LE, Ullrich O). We are also grateful for financial support from the DLR (grant no. 50WB1219, 50WB1519).

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Authors and Affiliations

  1. Institute of Anatomy, Faculty of Medicine, University of Zurich, Zurich, Switzerland

    Cora S. Thiel, Beatrice A. Lauber, Liliana E. Layer & Oliver Ullrich

  2. Department of Machine Design, Engineering Design and Product Development, Institute of Mechanical Engineering, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

    Cora S. Thiel & Oliver Ullrich

  3. Space Life Sciences Laboratory (SLSL), Kennedy Space Center, Merritt Island, FL, USA

    Oliver Ullrich

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  1. Cora S. Thiel
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  2. Beatrice A. Lauber
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  3. Liliana E. Layer
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  4. Oliver Ullrich
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Correspondence to Cora S. Thiel or Oliver Ullrich .

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  1. Health College of Pharmacy , University of South Florida, Tampa, FL, USA

    Yashwant Pathak

  2. PUCRS , Partenon, Porto Alegre, Rio Grande do Sul, Brazil

    Marlise Araújo dos Santos

  3. BioServe Space Technologies , University of Colorado, Boulder, CO, USA

    Luis Zea

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  1. Porto Alegre, Rio Grande do Sul, Brazil

    Marlise Araújo dos Santos

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Thiel, C.S., Lauber, B.A., Layer, L.E., Ullrich, O. (2019). Effects of Spaceflight on the Immune System. In: Pathak, Y., Araújo dos Santos, M., Zea, L. (eds) Handbook of Space Pharmaceuticals. Springer, Cham. https://doi.org/10.1007/978-3-319-50909-9_23-1

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