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Published in: Infection 4/2015

01-08-2015 | Review

Sex differences in immune responses to infectious diseases

Authors: Julia Fischer, Norma Jung, Nirmal Robinson, Clara Lehmann

Published in: Infection | Issue 4/2015

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Abstract

Purpose

The influence of sex hormones is recognized to account for the susceptibility and distinct outcomes of diverse infectious diseases.

Methods

This review discusses several variables including differences in behavior and exposure to pathogens, genetic, and immunological factors.

Conclusion

Understanding sex-based differences in immunity during different infectious diseases is crucial in order to provide optimal disease management for both sexes.

Literature
  1. Garenne M. Demographic evidence of sex differences in vulnerability to infectious diseases. J Infect Dis. 2015;211:331–2.PubMed CentralPubMedView Article
  2. Klein SL. Sex differences in prophylaxis and therapeutic treatments for viral diseases. Handb Exp Pharmacol. 2012;214:499–522.PubMedView Article
  3. Markle JG, Fish EN. SeXX matters in immunity. Trends Immunol. 2014;35:97–104.PubMedView Article
  4. Amur S, Parekh A, Mummaneni P. Sex differences and genomics in autoimmune diseases. J Autoimmun. 2012;38:J254–65.PubMedView Article
  5. Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol. 2010;10:594–604.PubMedView Article
  6. Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008;8:737–44.PubMedView Article
  7. Pinheiro I, Dejager L, Libert C. X-chromosome-located microRNAs in immunity: might they explain male/female differences? The X chromosome-genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females. BioEssays. 2011;33:791–802.PubMedView Article
  8. Hewagama A, Gorelik G, Patel D, Liyanarachchi P, McCune WJ, Somers E, et al. Overexpression of X-linked genes in T cells from women with lupus. J Autoimmun. 2013;41:60–71.PubMed CentralPubMedView Article
  9. Brooks EG, Schmalstieg FC, Wirt DP, Rosenblatt HM, Adkins LT, Lookingbill DP, et al. A novel X-linked combined immunodeficiency disease. J Clin Invest. 1990;86:1623–31.PubMed CentralPubMedView Article
  10. Schmalstieg FC, Goldman AS. Immune consequences of mutations in the human common gamma-chain gene. Mol Genet Metab. 2002;76:163–71.PubMedView Article
  11. van der Vliet HJ, Nieuwenhuis EE. IPEX as a result of mutations in FOXP3. Clin Dev Immunol. 2007;2007:89017.PubMed CentralPubMed
  12. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev. 2007;87:905–31.PubMedView Article
  13. Castles CG, Oesterreich S, Hansen R, Fuqua SA. Auto-regulation of the estrogen receptor promoter. J Steroid Biochem Mol Biol. 1997;62:155–63.PubMedView Article
  14. Shim GJ, Kis LL, Warner M, Gustafsson JA. Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene. Proc Natl Acad Sci USA. 2004;101:1720–4.PubMed CentralPubMedView Article
  15. Shim GJ, Wang L, Andersson S, Nagy N, Kis LL, Zhang Q, et al. Disruption of the estrogen receptor beta gene in mice causes myeloproliferative disease resembling chronic myeloid leukemia with lymphoid blast crisis. Proc Natl Acad Sci USA. 2003;100:6694–9.PubMed CentralPubMedView Article
  16. Lambert KC, Curran EM, Judy BM, Milligan GN, Lubahn DB, Estes DM. Estrogen receptor alpha (ERalpha) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17beta-estradiol acts through ERalpha to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation. J Immunol. 2005;175:5716–23.PubMedView Article
  17. Gourdy P, Araujo LM, Zhu R, Garmy-Susini B, Diem S, Laurell H, et al. Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN-gamma production by invariant natural killer T cells. Blood. 2005;105:2415–20.PubMedView Article
  18. Angele MK, Schwacha MG, Ayala A, Chaudry IH. Effect of gender and sex hormones on immune responses following shock. Shock. 2000;14:81–90.PubMedView Article
  19. Sader MA, McGrath KC, Hill MD, Bradstock KF, Jimenez M, Handelsman DJ, et al. Androgen receptor gene expression in leucocytes is hormonally regulated: implications for gender differences in disease pathogenesis. Clin Endocrinol (Oxf). 2005;62:56–63.View Article
  20. Medina KL, Garrett KP, Thompson LF, Rossi MI, Payne KJ, Kincade PW. Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen. Nat Immunol. 2001;2:718–24.PubMedView Article
  21. Desquilbet L, Goujard C, Rouzioux C, Sinet M, Deveau C, Chaix ML, et al. Does transient HAART during primary HIV-1 infection lower the virological set-point? AIDS. 2004;18:2361–9.PubMed
  22. Moore AL, Kirk O, Johnson AM, Katlama C, Blaxhult A, Dietrich M, et al. Virologic, immunologic, and clinical response to highly active antiretroviral therapy: the gender issue revisited. J Acquir Immune Defic Syndr. 2003;32:452–61.PubMedView Article
  23. Collazos J, Asensi V, Cartón JA. Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART. AIDS. 2007;21:835–43.PubMedView Article
  24. Farzadegan H, Hoover DR, Astemborski J, Lyles CM, Margolick JB, Markham RB, et al. Sex differences in HIV-1 viral load and progression to AIDS. Lancet. 1998;352:1510–4.PubMedView Article
  25. Sterling TR. When should highly active antiretroviral therapy be initiated? Hopkins HIV Rep. 2001;13:11.
  26. Meier A, Chang JJ, Chan ES, Pollard RB, Sidhu HK, Kulkarni S, et al. Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med. 2009;15:955–9.PubMed CentralPubMedView Article
  27. Herbeuval JP, Grivel JC, Boasso A, Hardy AW, Chougnet C, Dolan MJ, et al. CD4+ T-cell death induced by infectious and noninfectious HIV-1: role of type 1 interferon-dependent, TRAIL/DR5-mediated apoptosis. Blood. 2005;106:3524–31.PubMed CentralPubMedView Article
  28. Sodora DL, Gettie A, Miller CJ, Marx PA. Vaginal transmission of SIV: assessing infectivity and hormonal influences in macaques inoculated with cell-free and cell-associated viral stocks. AIDS Res Hum Retroviruses. 1998;14:S119–23.PubMedView Article
  29. Grebely J, Page K, Sacks-Davis R, van der Loeff MS, Rice TM, Bruneau J, et al. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59:109–20.PubMed CentralPubMedView Article
  30. Rodríguez-Torres M, Ríos-Bedoya CF, Rodríguez-Orengo J, Fernández-Carbia A, Marxuach-Cuétara AM, López-Torres A, et al. Progression to cirrhosis in Latinos with chronic hepatitis C: differences in Puerto Ricans with and without human immunodeficiency virus coinfection and along gender. J Clin Gastroenterol. 2006;40:358–66.PubMedView Article
  31. Di Martino V, Lebray P, Myers RP, Pannier E, Paradis V, Charlotte F, et al. Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure. Hepatology. 2004;40:1426–33.PubMedView Article
  32. McClelland EE, Smith JM. Gender specific differences in the immune response to infection. Archivum Immunologiae et Therapiae Experimentalis. 2011;59:203–13.PubMedView Article
  33. Narasimhan P, Wood J, Macintyre CR, Mathai D. Risk factors for tuberculosis. Pulm Med. 2013;2013:828939.PubMed CentralPubMedView Article
  34. Guerra-Silveira F, Abad-Franch F. Sex bias in infectious disease epidemiology: patterns and processes. PLoS one. 2013;8:e62390.PubMed CentralPubMedView Article
  35. Frieden TR, Lerner BH, Rutherford BR. Lessons from the 1800s: tuberculosis control in the new millennium. Lancet. 2000;355:1088–92.PubMedView Article
  36. Clarke WG, Cochrane AL, Miall WE. Results of a chest x-ray survey in the Vale of Glamorgan; a study of an agricultural community. Tubercle. 1956;37:417–25.PubMedView Article
  37. Yamamoto Y, Saito H, Setogawa T, Tomioka H. Sex differences in host resistance to Mycobacterium marinum infection in mice. Infect Immun. 1991;59:4089–96.PubMed CentralPubMed
  38. Svanberg L. Effects of estrogen deficiency in women castrated when young. Acta Obstet Gynecol Scand Suppl. 1981;106:11–5.PubMed
  39. Curtis J, Turk JL. Resistance to subcutaneous infection with Mycobacterium lepraemurium is controlled by more than one gene. Infect Immun. 1984;43:925–30.PubMed CentralPubMed
  40. Demkow U, Filewska M, Michalowska-Mitczuk D, Kus J, Jagodzinski J, Zielonka T, et al. Heterogeneity of antibody response to myobacterial antigens in different clinical manifestations of pulmonary tuberculosis. J Physiol Pharmacol. 2007;58:117–27.PubMed
  41. Pope V, Larsen SA, Rice RJ, Goforth SN, Parham CE, Fears MB. Flow cytometric analysis of peripheral blood lymphocyte immunophenotypes in persons infected with Treponema pallidum. Clin Diagn Lab Immunol. 1994;1:121–4.PubMed CentralPubMed
  42. Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P, Becker L, et al. Gender bias in autoimmunity is influenced by microbiota. Immunity. 2013;39:400–12.PubMedView Article
  43. Bernin H, Lotter H. Sex bias in the outcome of human tropical infectious diseases: influence of steroid hormones. J Infect Dis. 2014;209:S107–13.PubMedView Article
  44. Petrin D, Delgaty K, Bhatt R, Garber G. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev. 1998;11:300–17.PubMed CentralPubMed
  45. Liesenfeld O, Nguyen TA, Pharke C, Suzuki Y. Importance of gender and sex hormones in regulation of susceptibility of the small intestine to peroral infection with Toxoplasma gondii tissue cysts. J Parasitol. 2001;87:1491–3.PubMedView Article
  46. Karami M, Doudi M, Setorki M. Assessing epidemiology of cutaneous leishmaniasis in Isfahan, Iran. J Vector Borne Dis. 2013;50:30–7.PubMed
  47. Satoskar A, Alexander J. Sex-determined susceptibility and differential IFN-gamma and TNF-alpha mRNA expression in DBA/2 mice infected with Leishmania mexicana. Immunology. 1995;84:1–4.PubMed CentralPubMed
  48. Brabin L, Brabin BJ. Parasitic infections in women and their consequences. Adv Parasitol. 1992;31:1–81.PubMedView Article
  49. Degu G, Mengistu G, Jones J. Some factors affecting prevalence of and immune responses to Schistosoma mansoni in schoolchildren in Gorgora, northwest Ethiopia. Ethiop Med J. 2002;40:345–52.PubMed
  50. Travi BL, Osorio Y, Melby PC, Chandrasekar B, Arteaga L, Saravia NG. Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp. Infect Immun. 2002;70:2288–96.PubMed CentralPubMedView Article
  51. Lezama-Dávila CM, Isaac-Márquez AP, Barbi J, Oghumu S, Satoskar AR. 17Beta-estradiol increases Leishmania mexicana killing in macrophages from DBA/2 mice by enhancing production of nitric oxide but not pro-inflammatory cytokines. Am J Trop Med Hyg. 2007;76:1125–7.PubMed CentralPubMed
  52. Clayton JA, Collins FS. Policy: NIH to balance sex in cell and animal studies. Nature. 2014;509:282–3.PubMedView Article
Metadata
Title
Sex differences in immune responses to infectious diseases
Authors
Julia Fischer
Norma Jung
Nirmal Robinson
Clara Lehmann
Publication date
01-08-2015
Publisher
Springer Berlin Heidelberg
Published in
Infection / Issue 4/2015
Print ISSN: 0300-8126
Electronic ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-015-0791-9

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