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The Hibernating Immune System

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Living in a Seasonal World

Abstract

Several physiological changes take place during hibernation, which are thought to allow animals to conserve energy and limit organ injury as might otherwise occur due to the physiological extremes of torpor and arousal. Significant changes occur in the immune system during torpor. The number of circulating leukocytes drops by ~90% during entrance into torpor and seems to be driven by low body temperature. Normal cell counts restore upon arousal. Recently, we demonstrated that clearance of circulating lymphocytes is due to retention in lymphoid organs caused by a reduced plasma level of sphingosine-1-phosphate (S1P). Besides its effects on leukocyte migration, hibernation affects complement function, phagocytosis capacity, cytokine production, lymphocyte proliferation, and antibody production. The reduced immune function might play a major role in the etiology of White Nose Syndrome (WNS) in hibernating bats. Further, the ability to induce a fully reversible state of immune suppression in humans might aid the treatment of several inflammatory and immune-mediated diseases. Unraveling the mechanisms underlying the reduced immune function during torpor will not only enhance fundamental knowledge about the immune system, but might also lead to the development of a strategy to limit mortality due to WNS.

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References

  • Andjus RK et al (1964) Influence of hibernation and of intermittent hypothermia on the formation of immune hemagglutinins in the ground squirrel. Ann Acad Sci Fenn Biol 71:26–36

    Google Scholar 

  • Arendt T et al (2003) Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals. J Neurosci 23:6972–6981

    PubMed  CAS  Google Scholar 

  • Arrich J et al (2009) Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev 4:CD004128

    Google Scholar 

  • Atanassov CL et al (1995) Anti-lymphoproliferative activity of brown adipose tissue of hibernating ground squirrels is mainly caused by AMP. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 112:93–100

    Article  PubMed  CAS  Google Scholar 

  • Barlow A et al (2009) Investigations into suspected white-nose syndrome in two bat species in Somerset. Vet Rec 165:481–482

    Article  PubMed  Google Scholar 

  • Beekhuizen H, van Furth R (1993) Monocyte adherence to human vascular endothelium. J Leukoc Biol 54:363–378

    PubMed  CAS  Google Scholar 

  • Belzer FO et al (1967) 24-hour and 72-hour preservation of canine kidneys. Lancet 2:536–538

    Article  PubMed  CAS  Google Scholar 

  • Blehert DS et al (2009) Bat white-nose syndrome: an emerging fungal pathogen? Science 323:227

    Article  PubMed  CAS  Google Scholar 

  • Bouma HR et al (2010a) Hibernation: the immune system at rest? J Leuk Biol 88:619–624

    Article  CAS  Google Scholar 

  • Bouma HR et al (2010b) Blood cell dynamics during hibernation in the European ground squirrel. Vet Immunol Immunopathol 136:319–323

    Article  PubMed  CAS  Google Scholar 

  • Bouma HR et al (2011) Low body temperature governs the decline of circulating lymphocytes during hibernation through sphingosine-1-phosphate. Proc Natl Acad Sci USA 108:2052–2057

    Article  PubMed  Google Scholar 

  • Briggs C et al (2000) New quantitative parameters on a recently introduced automated blood cell counter—the XE 2100. Clin Lab Haematol 22:345–350

    Article  PubMed  CAS  Google Scholar 

  • Buchen L (2010) Disease epidemic killing only US bats. Nature 463:144–145

    Article  PubMed  CAS  Google Scholar 

  • Carey HV (1990) Seasonal changes in mucosal structure and function in ground squirrel intestine. Am J Physiol 259:R385–R392

    PubMed  CAS  Google Scholar 

  • Carey HV et al (2003) Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153–1181

    PubMed  CAS  Google Scholar 

  • Carey HV, Martin SL (1996) Preservation of intestinal gene expression during hibernation. Am J Physiol 271:G804–G813

    PubMed  CAS  Google Scholar 

  • Carey HV, Sills NS (1992) Maintenance of intestinal nutrient transport during hibernation. Am J Physiol 263:R517–R523

    PubMed  CAS  Google Scholar 

  • Carey HV, Sills NS (1996) Hibernation enhances d-glucose uptake by intestinal brush border membrane vesicles in ground squirrels. J Comp Physiol B 166:254–261

    Article  PubMed  CAS  Google Scholar 

  • Drew KL et al (1999) Ascorbate and glutathione regulation in hibernating ground squirrels. Brain Res 851:1–8

    Article  PubMed  CAS  Google Scholar 

  • Fleck CC, Carey HV (2005) Modulation of apoptotic pathways in intestinal mucosa during hibernation. Am J Physiol Regul Integr Comp Physiol 289:R586–R595

    Article  PubMed  CAS  Google Scholar 

  • Frerichs KU et al (1994) Local cerebral blood flow during hibernation, a model of natural tolerance to “cerebral ischemia”. J Cereb Blood Flow Metab 14:193–205

    Article  PubMed  CAS  Google Scholar 

  • Galletti G, Cavallari A (1972) The thymus of marmots: spontaneous, natural seasonal thymectomy? Acta Anat (Basel) 83:593–605

    Article  CAS  Google Scholar 

  • Galluser M et al (1988) Adaptation of intestinal enzymes to seasonal and dietary changes in a hibernator: the European hamster (Cricetus cricetus). J Comp Physiol B 158:143–149

    Article  PubMed  CAS  Google Scholar 

  • Inkovaara P, Suomalainen P (1973) Studies on the physiology of the hibernating hedgehog. 18. On the leukocyte counts in the hedgehog’s intestine and lungs. Ann Acad Sci Fenn Biol 200:1–21

    PubMed  CAS  Google Scholar 

  • Jaroslow BN, Serrell BA (1972) Differential sensitivity to hibernation of early and late events in development of the immune response. J Exp Zool 181:111–116

    Article  PubMed  CAS  Google Scholar 

  • Kandefer-Szerszen M (1988) Interferon production in leukocytes of spotted sousliks—effect of hibernation on the interferon response in vitro. J Interf Res 8:95–103

    Article  CAS  Google Scholar 

  • Kenagy GJ et al (1989) Annual cycle of energy and time expenditure in a golden-mantled ground squirrel population. Oecologia 78:269

    Article  Google Scholar 

  • Kourliouros A et al (2010) Low cardiopulmonary bypass perfusion temperatures are associated with acute kidney injury following coronary artery bypass surgery. Eur J Cardiothorac Surg 37:704–709

    Article  PubMed  Google Scholar 

  • Kraehenbuhl JP, Neutra MR (1992) Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev 72:853–879

    PubMed  CAS  Google Scholar 

  • Kurtz CC, Carey HV (2007) Seasonal changes in the intestinal immune system of hibernating ground squirrels. Dev Comp Immunol 31:415–428

    Article  PubMed  CAS  Google Scholar 

  • Kurtz CC et al (2006) Hibernation confers resistance to intestinal ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 291:G895–G901

    Article  PubMed  CAS  Google Scholar 

  • Lindell SL et al (2005) Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype. Am J Physiol Gastrointest Liver Physiol 288:G473–G480

    Article  PubMed  CAS  Google Scholar 

  • Mandala S et al (2002) Alteration of lymphocyte trafficking by sphingosine-1-phosphatesphingosine-1-phosphate receptor agonists. Science 296:346–349

    Article  PubMed  CAS  Google Scholar 

  • Maniero GD (2002) Classical pathway serum complement activity throughout various stages of the annual cycle of a mammalian hibernator, the golden-mantled ground squirrel, Spermophilus lateralis. Dev Comp Immunol 26:563–574

    Article  PubMed  CAS  Google Scholar 

  • Maniero GD (2005) Ground squirrel splenic macrophagesmacrophages bind lipopolysaccharide over a wide range of temperatures at all phases of their annual hibernation cycle. Comp Immunol Microbiol Infect Dis 28:297–309

    Article  PubMed  Google Scholar 

  • Matloubian M et al (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355–360

    Article  PubMed  CAS  Google Scholar 

  • Morin P Jr et al (2008) Expression of Nrf2 and its downstream gene targets in hibernating 13-lined ground squirrels, Spermophilus tridecemlineatus. Mol Cell Biochem 312:121–129

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa M, Terashima T, D’yachkova Y, Bondy GP, Hogg JC, van Eeden SF (1998) Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes. Circulation 98:2307–2313

    PubMed  CAS  Google Scholar 

  • Novoselova EG et al (2000) Production of tumor necrosis factor in cells of hibernating ground squirrels Citellus undulatus during annual cycle. Life Sci 67:1073–1080

    Article  PubMed  CAS  Google Scholar 

  • Novoselova EG et al (2004) Effect of the transplanted thymus of hibernating ground squirrels on the age-related thymus involution in rats. Dokl Biol Sci 397:272–273

    Article  PubMed  CAS  Google Scholar 

  • Pappu R et al (2007) Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphatesphingosine-1-phosphate. Science 316:295–298

    Article  PubMed  CAS  Google Scholar 

  • Prendergast BJ et al (2002) Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels. Am J Physiol Regul Integr Comp Physiol 282:R1054–R1062

    PubMed  CAS  Google Scholar 

  • Puechmaille SJ et al (2010) White-nose syndrome fungus (Geomyces destructans) in bat, France. Emerg Infect Dis 16:290–293

    PubMed  CAS  Google Scholar 

  • Reznik G et al (1975) Comparative studies of blood from hibernating and nonhibernating European hamsters (Cricetus cricetus L). Lab Anim Sci 25:210–215

    PubMed  CAS  Google Scholar 

  • Ruzicka K et al (2001) The new hematology analyzer Sysmex XE-2100: performance evaluation of a novel white blood cell differential technology. Arch Pathol Lab Med 125:391–396

    PubMed  CAS  Google Scholar 

  • Salahudeen AK (2004) Consequences of cold ischemic injury of kidneys in clinical transplantation. J Investig Med 52:296–298

    PubMed  Google Scholar 

  • Sandovici M et al (2004) Differential regulation of glomerular and interstitial endothelial nitric oxide synthase expression in the kidney of hibernating ground squirrel. Nitric Oxide 11:194–200

    Article  PubMed  CAS  Google Scholar 

  • Shivatcheva TM (1988) Survival of skin allografts in European ground squirrels, Spermophilus citellus L., during hibernation. Folia Biol (Krakow) 36:213–221

    CAS  Google Scholar 

  • Spurrier WA, Dawe AR (1973) Several blood and circulatory changes in the hibernation of the 13-lined ground squirrel, Citellus tridecemlineatus. Comp Biochem Physiol A Comp Physiol 44:267–282

    Article  PubMed  CAS  Google Scholar 

  • Storey KB (2010) Out cold: biochemical regulation of mammalian hibernation—a mini-review. Gerontology 56:220–230

    Article  PubMed  Google Scholar 

  • Suomalainen P, Rosokivi V (1973) Studies on the physiology of the hibernating hedgehog. 17. The blood cell count of the hedgehog at different times of the year and in different phases of the hibernating cycle. Ann Acad Sci Fenn Biol 198:1–8

    PubMed  CAS  Google Scholar 

  • Szilagyi JE, Senturia JB (1972) A comparison of bone marrow leukocytes in hibernating and nonhibernating woodchucks and ground squirrels. Cryobiology 9:257–261

    Article  PubMed  CAS  Google Scholar 

  • Talaei F et al (2011) Reversible remodelling of lung tissue during hibernation in the Syrian hamster. J Exp Biol 214(pt8):1276–1282

    Article  PubMed  Google Scholar 

  • Terasaki PI et al (1996) Fit and match hypothesis for kidney transplantation. Transplantation 62:441–445

    Article  PubMed  CAS  Google Scholar 

  • Toien O et al (2001) Ascorbate dynamics and oxygen consumption during arousal from hibernation in Arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol 281:R572–R583

    PubMed  CAS  Google Scholar 

  • Ulevitch RJ, Tobias PS (1999) Recognition of gram-negative bacteria and endotoxin by the innate immune system. Curr Opin Immunol 11:19–22

    Article  PubMed  CAS  Google Scholar 

  • van Breukelen F et al (2010) Vertebrate cell death in energy-limited conditions and how to avoid it: what we might learn from mammalian hibernators and other stress-tolerant vertebrates. Apoptosis 15:386–399

    Article  PubMed  Google Scholar 

  • von Vietinghoff S, Ley K (2008) Homeostatic regulation of blood neutrophil counts. J Immunol 181:5183–5188

    Google Scholar 

  • Wibbelt G et al (2010) Emerging diseases in Chiroptera: why bats? Biol Lett 6:438–440

    Google Scholar 

  • Woof JM, Mestecky J (2005) Mucosal immunoglobulins. Immunol Rev 206:64–82

    Article  PubMed  CAS  Google Scholar 

  • Zancanaro C et al (1999) The kidney during hibernation and arousal from hibernation. A natural model of organ preservation during cold ischemia and reperfusion. Neprol Dial Transplant 14:1982–1990

    Article  CAS  Google Scholar 

  • Zimmerman R (2009) Ecology. Biologists struggle to solve bat deaths. Science 324:1134–1135

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University Medical Center Groningen, Antonius Deusinglaan 1/FB20, 9713 AV Groningen, Groningen, The Netherlands

    Hjalmar R. Bouma, Arjen M. Strijkstra, Fatimeh Talaei & Rob H. Henning

  2. Department of Animal Behavior/Chronobiology, University of Groningen, Groningen, The Netherlands

    Hjalmar R. Bouma & Arjen M. Strijkstra

  3. Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA

    Hannah V. Carey

  4. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Frans G. M. Kroese

Authors
  1. Hjalmar R. Bouma
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  2. Arjen M. Strijkstra
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  3. Fatimeh Talaei
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  4. Rob H. Henning
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  5. Hannah V. Carey
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  6. Frans G. M. Kroese
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Correspondence to Hjalmar R. Bouma .

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Editors and Affiliations

  1. Forschungsinst. Wildtierkunde und, Ökologie, Veterinärmedizinische Universität Wien, Veterinärplatz 1, Wien, 1210, Austria

    Thomas Ruf

  2. Research Institute of Wildlife Ecology, Savoyenstr. 1, Vienna, 1160, Austria

    Claudia Bieber

  3. Research Institute of Wildlife Ecology, Savoyenstr. 1, Vienna, 1160, Austria

    Walter Arnold

  4. , Dept. of Behavioural Biology, University of Vienna, Althanstr. 14, Vienna, 1160, Austria

    Eva Millesi

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Bouma, H.R., Strijkstra, A.M., Talaei, F., Henning, R.H., Carey, H.V., Kroese, F.G. (2012). The Hibernating Immune System. In: Ruf, T., Bieber, C., Arnold, W., Millesi, E. (eds) Living in a Seasonal World. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28678-0_23

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