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Androgen-dependent immune modulation in parasitic infection

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Abstract

Parasitic infections modulate the immune system of the host, resulting in either immune tolerance or the induction of pro-inflammatory defense mechanisms against the pathogen. In both cases, sex hormones are involved in the regulation of the immune response, as they are present in the systemic circulation and can act on a wide variety of cell types, including immune cells. Men and women have a different milieu of sex hormones, and these hormones play a role in determining immune responses to parasitic infections. Men, who have higher plasma levels of androgens than women, are generally more susceptible to parasitic infections. Many immune cells express the androgen receptor (AR), and the immunologic functions of these cells can be modulated by androgens. In this review, we will highlight the immune cell types that are sensitive to male steroid hormones and describe their roles during three parasitic diseases, amebiasis, leishmaniasis, and helminthiasis.

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References

  1. Roberts CW, Walker W, Alexander J (2001) Sex-associated hormones and immunity to protozoan parasites. Clin Microbiol Rev 14(3):476–488. https://doi.org/10.1128/CMR.14.3.476-488.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. L KS (2004) Hormonal and immunological mechanisms mediating sex differences in parasite infection. Parasite Immunol 26(6–7):247–264. https://doi.org/10.1111/j.0141-9838.2004.00710.x

    Article  Google Scholar 

  3. Nava-Castro K, Hernandez-Bello R, Muniz-Hernandez S, Camacho-Arroyo I, Morales-Montor J (2012) Sex steroids, immune system, and parasitic infections: facts and hypotheses. Ann N Y Acad Sci 1262:16–26. https://doi.org/10.1111/j.1749-6632.2012.06632.x

    Article  CAS  PubMed  Google Scholar 

  4. Bernin H, Marggraff C, Jacobs T, Brattig N, Le VA, Blessmann J et al (2014) Immune markers characteristic for asymptomatically infected and diseased Entamoeba histolytica individuals and their relation to sex. BMC Infect Dis 14:621. https://doi.org/10.1186/s12879-014-0621-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Duneau D, Ebert D (2012) Host sexual dimorphism and parasite adaptation. PLoS Biol 10(2):e1001271. https://doi.org/10.1371/journal.pbio.1001271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Eggers S, Ohnesorg T, Sinclair A (2014) Genetic regulation of mammalian gonad development. Nat Rev Endocrinol 10(11):673–683. https://doi.org/10.1038/nrendo.2014.163

    Article  CAS  PubMed  Google Scholar 

  7. Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic for Sry. Nature 351:117. https://doi.org/10.1038/351117a0

    Article  CAS  PubMed  Google Scholar 

  8. Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ et al (1990) A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346:240. https://doi.org/10.1038/346240a0

    Article  CAS  PubMed  Google Scholar 

  9. Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al (2018) TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol 3(19). https://doi.org/10.1126/sciimmunol.aap8855

  10. Libert C, Dejager L, Pinheiro I (2010) The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol 10(8):594–604. https://doi.org/10.1038/nri2815

    Article  CAS  PubMed  Google Scholar 

  11. Kovats S, Carreras E, Agrawal H (2010) Sex steroid receptors in immune cells. Springer-Verlag, Berlin, pp 53–91

    Google Scholar 

  12. Lotter H, Helk E, Bernin H, Jacobs T, Prehn C, Adamski J et al (2013) Testosterone increases susceptibility to amebic liver abscess in mice and mediates inhibition of IFNgamma secretion in natural killer T cells. PLoS One 8(2):e55694. https://doi.org/10.1371/journal.pone.0055694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sanderson JT (2006) The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicol Sci 94(1):3–21. https://doi.org/10.1093/toxsci/kfl051

    Article  CAS  PubMed  Google Scholar 

  14. Miller WL, Auchus RJ (2011) The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 32(1):81–151. https://doi.org/10.1210/er.2010-0013

    Article  PubMed  Google Scholar 

  15. Marchetti PM, Barth JH (2013) Clinical biochemistry of dihydrotestosterone. Ann Clin Biochem 50(2):95–107. https://doi.org/10.1258/acb.2012.012159

    Article  CAS  PubMed  Google Scholar 

  16. Trottmann M, Dickmann M, Stief CG, Becker AJ (2010) Laboratory work-up of testosterone. Der Urologe Ausg A 49(1):11–15. https://doi.org/10.1007/s00120-009-2192-0

    Article  CAS  PubMed  Google Scholar 

  17. Davey RA, Grossmann M (2016) Androgen receptor structure, function and biology: from bench to bedside. Clin Biochem Rev 37(1):3–15

    PubMed  PubMed Central  Google Scholar 

  18. Torjesen PA, Sandnes L (2004) Serum testosterone in women as measured by an automated immunoassay and a RIA. Clin Chem 50(3):678; author reply −9. https://doi.org/10.1373/clinchem.2003.027565

    Article  CAS  PubMed  Google Scholar 

  19. Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y et al (2017) Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the United States and Europe. J Clin Endocrinol Metabol 102(4):1161–1173. https://doi.org/10.1210/jc.2016-2935

    Article  Google Scholar 

  20. Finkelstein JS, Lee H, Burnett-Bowie S-AM, Pallais JC, Yu EW, Borges LF et al (2013) Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med 369(11):1011–1022. https://doi.org/10.1056/NEJMoa1206168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Barbieri JFSRL (2009) Yen and Jaffe’s reproductive endocrinology: physiology, pathophysiology, and clinical management. : Elsevier Health Sciences

  22. Kameda T, Mano H, Yuasa T, Mori Y, Miyazawa K, Shiokawa M et al (1997) Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med 186(4):489–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Alan H. Decherney LN, Laufer N, Roman AS (2013) Current diagnosis & treatment; Obstetrics & Gynecology, 11th ed. The McGraw-Hill Companies

  24. Progesterone NIH (2011) Clinical center test guide. Available from: https://web.archive.org/web/20150701024923/http://cclnprod.cc.nih.gov/dlm/testguide.nsf/0/CB26894E1EB28DEF85256BA5005B000E?OpenDocument

  25. Oettel M, Mukhopadhyay AK (2004) Progesterone: the forgotten hormone in men? Aging Male 7(3):236–257. https://doi.org/10.1080/13685530400004199

    Article  CAS  PubMed  Google Scholar 

  26. Reddy DS (2010) Neurosteroids: endogenous role in the human brain and therapeutic potentials. Prog Brain Res 186:113–137. https://doi.org/10.1016/B978-0-444-53630-3.00008-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Arriza J, Weinberger C, Cerelli G, Glaser T, Handelin B, Housman D et al (1987) Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science (New York, NY) 237(4812):268–275. https://doi.org/10.1126/science.3037703

    Article  CAS  Google Scholar 

  28. Dressing GE, Goldberg JE, Charles NJ, Schwertfeger KL, Lange CA (2011) Membrane progesterone receptor expression in mammalian tissues; a review of regulation and physiological implications. Steroids 76(1–2):11–17. https://doi.org/10.1016/j.steroids.2010.09.006

    Article  CAS  PubMed  Google Scholar 

  29. Schulster M, Bernie AM, Ramasamy R (2016) The role of estradiol in male reproductive function. Asian J Androl 18(3):435–440. https://doi.org/10.4103/1008-682X.173932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wahlin-Jacobsen S, Pedersen AT, Kristensen E, Laessoe NC, Lundqvist M, Cohen AS et al (2015) Is there a correlation between androgens and sexual desire in women? J Sex Med 12(2):358–373. https://doi.org/10.1111/jsm.12774

    Article  CAS  PubMed  Google Scholar 

  31. Randolph JF Jr, Zheng H, Avis NE, Greendale GA, Harlow SD (2015) Masturbation frequency and sexual function domains are associated with serum reproductive hormone levels across the menopausal transition. J Clin Endocrinol Metab 100(1):258–266. https://doi.org/10.1210/jc.2014-1725

    Article  CAS  PubMed  Google Scholar 

  32. McEwen BS (1981) Neural gonadal steroid actions. Science (New York, NY) 211(4488):1303–1311

    Article  CAS  Google Scholar 

  33. Wilson CM, McPhaul MJ (1996) A and B forms of the androgen receptor are expressed in a variety of human tissues. Mol Cell Endocrinol 120(1):51–57

    Article  CAS  PubMed  Google Scholar 

  34. Davis SR, Wahlin-Jacobsen S (2015) Testosterone in women_the clinical significance. Lancet Diabetes Endocrinol 3(12):980–992. https://doi.org/10.1016/S2213-8587(15)00284-3

    Article  CAS  PubMed  Google Scholar 

  35. Herold DA, Fitzgerald RL (2003) Immunoassays for testosterone in women: better than a guess? Clin Chem 49(8):1250–1251

    Article  CAS  PubMed  Google Scholar 

  36. Harwood DT, Handelsman DJ (2009) Development and validation of a sensitive liquid chromatography-tandem mass spectrometry assay to simultaneously measure androgens and estrogens in serum without derivatization. Clin Chim Acta 409(1–2):78–84. https://doi.org/10.1016/j.cca.2009.09.003

    Article  CAS  PubMed  Google Scholar 

  37. Fish EN (2008) The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 8(9):737–744. https://doi.org/10.1038/nri2394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gourdy P, Araujo LM, Zhu R, Garmy-Susini B, Diem S, Laurell H et al (2005) Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN-gamma production by invariant natural killer T cells. Blood 105(6):2415–2420. https://doi.org/10.1182/blood-2004-07-2819

    Article  CAS  PubMed  Google Scholar 

  39. Asai K, Hiki N, Mimura Y, Ogawa T, Unou K, Kaminishi M (2001) Gender differences in cytokine secretion by human peripheral blood mononuclear cells: role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model. Shock (Augusta, Ga) 16(5):340–343

    Article  CAS  Google Scholar 

  40. Gubbels Bupp MR, Jorgensen TN (2018) Androgen-induced immunosuppression. Front Immunol 9:794. https://doi.org/10.3389/fimmu.2018.00794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Viselli SM, Reese KR, Fan J, Kovacs WJ, Olsen NJ (1997) Androgens alter B cell development in normal male mice. Cell Immunol 182(2):99–104. https://doi.org/10.1006/cimm.1997.1227

    Article  CAS  PubMed  Google Scholar 

  42. Loy CJ, Sim KS, Yong EL (2003) Filamin-A fragment localizes to the nucleus to regulate androgen receptor and coactivator functions. Proc Natl Acad Sci U S A 100(8):4562–4567. https://doi.org/10.1073/pnas.0736237100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shatkina L, Mink S, Rogatsch H, Klocker H, Langer G, Nestl A et al (2003) The cochaperone Bag-1L enhances androgen receptor action via interaction with the NH2-terminal region of the receptor. Mol Cell Biol 23(20):7189–7197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Simental JA, Sar M, Lane MV, French FS, Wilson EM (1991) Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem 266(1):510–518

    CAS  PubMed  Google Scholar 

  45. De Toni L, Guidolin D, De Filippis V, Tescari S, Strapazzon G, Santa Rocca M et al (2016) Osteocalcin and sex hormone binding globulin compete on a specific binding site of GPRC6A. Endocrinology 157(11):4473–4486. https://doi.org/10.1210/en.2016-1312

    Article  CAS  PubMed  Google Scholar 

  46. Pi M, Parrill AL, Quarles LD (2010) GPRC6A mediates the non-genomic effects of steroids. J Biol Chem 285(51):39953–39964. https://doi.org/10.1074/jbc.M110.158063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC (2010) Molecular cell biology of androgen receptor signalling. Int J Biochem Cell Biol 42(6):813–827. https://doi.org/10.1016/j.biocel.2009.11.013

    Article  CAS  PubMed  Google Scholar 

  48. Nadiminty N, Lou W, Sun M, Chen J, Yue J, Kung HJ et al (2010) Aberrant activation of the androgen receptor by NF-kappaB2/p52 in prostate cancer cells. Cancer Res 70(8):3309–3319. https://doi.org/10.1158/0008-5472.can-09-3703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. McCall P, Bennett L, Ahmad I, Mackenzie LM, Forbes IW, Leung HY et al (2012) NFkappaB signalling is upregulated in a subset of castrate-resistant prostate cancer patients and correlates with disease progression. Br J Cancer 107(9):1554–1563. https://doi.org/10.1038/bjc.2012.372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhang L, Altuwaijri S, Deng F, Chen L, Lal P, Bhanot UK et al (2009) NF-kappaB regulates androgen receptor expression and prostate cancer growth. Am J Pathol 175(2):489–499. https://doi.org/10.2353/ajpath.2009.080727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lessard L, Begin LR, Gleave ME, Mes-Masson AM, Saad F (2005) Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study. Br J Cancer 93(9):1019–1023. https://doi.org/10.1038/sj.bjc.6602796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sharma NL, Massie CE, Ramos-Montoya A, Zecchini V, Scott HE, Lamb AD et al (2013) The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man. Cancer Cell 23(1):35–47. https://doi.org/10.1016/j.ccr.2012.11.010

    Article  CAS  PubMed  Google Scholar 

  53. Thomas C, Zoubeidi A, Kuruma H, Fazli L, Lamoureux F, Beraldi E et al (2011) Transcription factor Stat5 knockdown enhances androgen receptor degradation and delays castration-resistant prostate cancer progression in vivo. Mol Cancer Ther 10(2):347–359. https://doi.org/10.1158/1535-7163.mct-10-0850

    Article  CAS  PubMed  Google Scholar 

  54. Sahu B, Laakso M, Ovaska K, Mirtti T, Lundin J, Rannikko A et al (2011) Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer. EMBO J 30(19):3962–3976. https://doi.org/10.1038/emboj.2011.328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP et al (2012) The mutational landscape of lethal castration-resistant prostate cancer. Nature 487(7406):239–243. https://doi.org/10.1038/nature11125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Liu Y, Carlsson R, Comabella M, Wang J, Kosicki M, Carrion B et al (2014) FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS. Nat Med 20(3):272–282. https://doi.org/10.1038/nm.3485

    Article  CAS  PubMed  Google Scholar 

  57. Liu Y, Marin A, Ejlerskov P, Rasmussen LM, Prinz M, Issazadeh-Navikas S (2017) Neuronal IFN-beta-induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1(+)Treg cells. Nat Commun 8:14709. https://doi.org/10.1038/ncomms14709

    Article  PubMed  PubMed Central  Google Scholar 

  58. Schuurs AH, Verheul HA (1990) Effects of gender and sex steroids on the immune response. J Steroid Biochem 35(2):157–172

    Article  CAS  PubMed  Google Scholar 

  59. Ibanez L, Jaramillo AM, Ferrer A, de Zegher F (2005) High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception. Hum Reprod 20(9):2457–2462. https://doi.org/10.1093/humrep/dei072

    Article  CAS  PubMed  Google Scholar 

  60. Chuang KH, Altuwaijri S, Li G, Lai JJ, Chu CY, Lai KP et al (2009) Neutropenia with impaired host defense against microbial infection in mice lacking androgen receptor. J Exp Med 206(5):1181–1199. https://doi.org/10.1084/jem.20082521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Marin DP, Bolin AP, dos Santos RC, Curi R, Otton R (2010) Testosterone suppresses oxidative stress in human neutrophils. Cell Biochem Funct 28(5):394–402. https://doi.org/10.1002/cbf.1669

    Article  CAS  PubMed  Google Scholar 

  62. Benten WP, Lieberherr M, Stamm O, Wrehlke C, Guo Z, Wunderlich F (1999) Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages. Mol Biol Cell 10(10):3113–3123. https://doi.org/10.1091/mbc.10.10.3113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Rettew JA, Huet-Hudson YM, Marriott I (2008) Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod 78(3):432–437. https://doi.org/10.1095/biolreprod.107.063545

    Article  CAS  PubMed  Google Scholar 

  64. Ashcroft GS, Mills SJ (2002) Androgen receptor-mediated inhibition of cutaneous wound healing. J Clin Invest 110(5):615–624. https://doi.org/10.1172/jci15704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Goncalves RV, Novaes RD, Sarandy MM, Damasceno EM, da Matta SL, de Gouveia NM et al (2016) 5alpha-dihydrotestosterone enhances wound healing in diabetic rats. Life Sci 152:67–75. https://doi.org/10.1016/j.lfs.2016.03.019

    Article  CAS  PubMed  Google Scholar 

  66. Kanda N, Tsuchida T, Tamaki K (1996) Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells. Clin Exp Immunol 106(2):410–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Schwarz E, Schafer C, Bode JC, Bode C (2000) Influence of the menstrual cycle on the LPS-induced cytokine response of monocytes. Cytokine 12(4):413–416. https://doi.org/10.1006/cyto.1999.0570

    Article  CAS  PubMed  Google Scholar 

  68. Bouman A, Schipper M, Heineman MJ, Faas MM (2004) Gender difference in the non-specific and specific immune response in humans. Am J Reprod Immunol 52(1):19–26. https://doi.org/10.1111/j.1600-0897.2004.00177.x

    Article  PubMed  Google Scholar 

  69. Paharkova-Vatchkova V, Maldonado R, Kovats S (2004) Estrogen preferentially promotes the differentiation of CD11c+ CD11 (intermediate) dendritic cells from bone marrow precursors. J Immunol 172(3):1426

    Article  CAS  PubMed  Google Scholar 

  70. Lin AA, Wojciechowski SE, Hildeman DA (2010) Androgens suppress antigen-specific T cell responses and IFN-γ production during intracranial LCMV infection. J Neuroimmunol 226:8–19. https://doi.org/10.1016/j.jneuroim.2010.05.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Koh YT, Gray A, Higgins SA, Hubby B, Kast WM (2009) Androgen ablation augments prostate cancer vaccine immunogenicity only when applied after immunization. Prostate 69(6):571–584. https://doi.org/10.1002/pros.20906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL, Thiebaut R et al (2014) Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A 111(2):869–874. https://doi.org/10.1073/pnas.1321060111

    Article  CAS  PubMed  Google Scholar 

  73. Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16(10):626–638. https://doi.org/10.1038/nri.2016.90

    Article  CAS  PubMed  Google Scholar 

  74. Wilhelmson AS, Lantero Rodriguez M, Stubelius A, Fogelstrand P, Johansson I, Buechler MB et al (2018) Testosterone is an endogenous regulator of BAFF and splenic B cell number. Nat Commun 9(1):2067. https://doi.org/10.1038/s41467-018-04408-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mackay F, Schneider P (2009) Cracking the BAFF code. Nat Rev Immunol 9(7):491–502. https://doi.org/10.1038/nri2572

    Article  CAS  PubMed  Google Scholar 

  76. Benten WP, Becker A, Schmitt-Wrede HP, Wunderlich F (2002) Developmental regulation of intracellular and surface androgen receptors in T cells. Steroids 67(11):925–931

    Article  CAS  PubMed  Google Scholar 

  77. Kovacs WJ, Olsen NJ (1987) Androgen receptors in human thymocytes. J Immunol 139(2):490–493

    CAS  PubMed  Google Scholar 

  78. Olsen NJ, Kovacs JW (1989) Increased thymic size and thymocyte interleukin 2 production in androgen-resistant mice. Scand J Immunol 29(6):733–738. https://doi.org/10.1111/j.1365-3083.1989.tb01178.x

    Article  CAS  PubMed  Google Scholar 

  79. Greenstein BD, Fitzpatrick FT, Adcock IM, Kendall MD, Wheeler MJ (1986) Reappearance of the thymus in old rats after orchidectomy: inhibition of regeneration by testosterone. J Endocrinol 110(3):417–422

    Article  CAS  PubMed  Google Scholar 

  80. Zhu ML, Bakhru P, Conley B, Nelson JS, Free M, Martin A et al (2016) Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator. Nat Commun 7:11350. https://doi.org/10.1038/ncomms11350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Olsen NJ, Zhou P, Ong H, Kovacs WJ (1993) Testosterone induces expression of transforming growth factor-beta1 in the murine thymus. J Steroid Biochem Mol Biol 45(5):327–332. https://doi.org/10.1016/0960-0760(93)90001-D

    Article  CAS  PubMed  Google Scholar 

  82. McMurray RW, Suwannaroj S, Ndebele K, Jenkins JK (2001) Differential effects of sex steroids on T and B cells: modulation of cell cycle phase distribution, apoptosis and bcl-2 protein levels. Pathobiology 69(1):44–58. https://doi.org/10.1159/000048757

    Article  CAS  PubMed  Google Scholar 

  83. Liva SM, Voskuhl RR (2001) Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production. J Immunol 167(4):2060–2067

    Article  CAS  PubMed  Google Scholar 

  84. Massa MG, David C, Jörg S, Berg J, Gisevius B, Hirschberg S et al (2017) Testosterone differentially affects T cells and neurons in murine and human models of neuroinflammation and neurodegeneration. Am J Pathol 187(7):1613–1622. https://doi.org/10.1016/j.ajpath.2017.03.006

    Article  CAS  PubMed  Google Scholar 

  85. Fijak M, Schneider E, Klug J, Bhushan S, Hackstein H, Schuler G et al (2011) Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: evidence for a direct role of testosterone on regulatory T cell expansion. J Immunol 186(9):5162

    Article  CAS  PubMed  Google Scholar 

  86. Kissick HT, Sanda MG, Dunn LK, Pellegrini KL, On ST, Noel JK et al (2014) Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc Natl Acad Sci 111(27):9887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Roved J, Westerdahl H, Hasselquist D (2017) Sex differences in immune responses: hormonal effects, antagonistic selection, and evolutionary consequences. Horm Behav 88:95–105. https://doi.org/10.1016/j.yhbeh.2016.11.017

    Article  CAS  PubMed  Google Scholar 

  88. Walecki M, Eisel F, Klug J, Baal N, Paradowska-Dogan A, Wahle E et al (2015) Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells. Mol Biol Cell 26(15):2845–2857. https://doi.org/10.1091/mbc.E14-08-1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ximenez C, Moran P, Rojas L, Valadez A, Gomez A (2009) Reassessment of the epidemiology of amebiasis: state of the art. Infect Genet Evol 9(6):1023–1032. https://doi.org/10.1016/j.meegid.2009.06.008

    Article  PubMed  Google Scholar 

  90. Parasites - Amebiasis - Entamoeba histolytica Infection: Centers for Disease Control and Prevention; 2015 [cited 2018 August 28]. Available from: https://www.cdc.gov/parasites/amebiasis/pathogen.html

  91. Blessmann J, Van Linh P, Nu PA, Thi HD, Muller-Myhsok B, Buss H et al (2002) Epidemiology of amebiasis in a region of high incidence of amebic liver abscess in central Vietnam. Am J Trop Med Hyg 66(5):578–583

    Article  PubMed  Google Scholar 

  92. Acuna-Soto R, Maguire JH, Wirth DF (2000) Gender distribution in asymptomatic and invasive amebiasis. Am J Gastroenterol 95(5):1277–1283. https://doi.org/10.1111/j.1572-0241.2000.01525.x

    Article  CAS  PubMed  Google Scholar 

  93. McGarr PL, Madiba TE, Thomson SR, Corr P (2003) Amoebic liver abscess--results of a conservative management policy. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 93(2):132–136

    CAS  PubMed  Google Scholar 

  94. Herbinger KH, Fleischmann E, Weber C, Perona P, Loscher T, Bretzel G (2011) Epidemiological, clinical, and diagnostic data on intestinal infections with Entamoeba histolytica and Entamoeba dispar among returning travelers. Infection 39(6):527–535. https://doi.org/10.1007/s15010-011-0155-z

    Article  PubMed  Google Scholar 

  95. Lotter H, Jacobs T, Gaworski I, Tannich E (2006) Sexual dimorphism in the control of amebic liver abscess in a mouse model of disease. Infect Immun 74(1):118–124. https://doi.org/10.1128/iai.74.1.118-124.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Helk E, Bernin H, Ernst T, Ittrich H, Jacobs T, Heeren J et al (2013) TNFalpha-mediated liver destruction by Kupffer cells and Ly6Chi monocytes during Entamoeba histolytica infection. PLoS Pathog 9(1):e1003096. https://doi.org/10.1371/journal.ppat.1003096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Noll J, Helk E, Fehling H, Bernin H, Marggraff C, Jacobs T et al (2016) IL-23 prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage. J Hepatol 64(5):1147–1157. https://doi.org/10.1016/j.jhep.2016.01.013

    Article  CAS  PubMed  Google Scholar 

  98. Seydel KB, Smith SJ, Stanley SL Jr (2000) Innate immunity to amebic liver abscess is dependent on gamma interferon and nitric oxide in a murine model of disease. Infect Immun 68(1):400–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lotter H, Gonzalez-Roldan N, Lindner B, Winau F, Isibasi A, Moreno-Lafont M et al (2009) Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess. PLoS Pathog 5(5):e1000434. https://doi.org/10.1371/journal.ppat.1000434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bernin H, Fehling H, Marggraff C, Tannich E, Lotter H (2016) The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus. Med Microbiol Immunol 205(4):321–332. https://doi.org/10.1007/s00430-016-0449-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Prevention CfDCa. Leishmaniasis 2018 [cited December 14, 2017]. Available from: https://www.cdc.gov/dpdx/leishmaniasis/index.html

  102. Horrillo L, San Martin JV, Molina L, Madronal E, Matia B, Castro A et al (2015) Atypical presentation in adults in the largest community outbreak of leishmaniasis in Europe (Fuenlabrada, Spain). Clin Microbiol Infect 21(3):269–273. https://doi.org/10.1016/j.cmi.2014.10.017

    Article  CAS  PubMed  Google Scholar 

  103. Leishmaniasis: World Health Organisation; 2018 [cited 2018 July 9th]. Available from: http://www.who.int/gho/neglected_diseases/leishmaniasis/en/

  104. Alexander J, Satoskar AR, Russell DG (1999) Leishmania species: models of intracellular parasitism. J Cell Sci 112(Pt 18):2993–3002

    CAS  PubMed  Google Scholar 

  105. Moein D, Masoud D, Saeed M, Abbas D (2018) Epidemiological aspects of cutaneous leishmaniasis during 2009-2016 in Kashan City, Central Iran. Korean J Parasitol 56(1):21–24. https://doi.org/10.3347/kjp.2018.56.1.21

    Article  PubMed  PubMed Central  Google Scholar 

  106. Eid D, Guzman-Rivero M, Rojas E, Goicolea I, Hurtig AK, Illanes D et al (2018) Risk factors for cutaneous leishmaniasis in the rainforest of Bolivia: a cross-sectional study. Trop Med Health 46:9. https://doi.org/10.1186/s41182-018-0089-6

    Article  PubMed  PubMed Central  Google Scholar 

  107. Rodriguez NE, Lima ID, Gaur Dixit U, Turcotte EA, Lockard RD, Batra-Sharma H et al (2018) Epidemiological and experimental evidence for sex-dependent differences in the outcome of Leishmania infantum infection. Am J Trop Med Hyg 98(1):142–145. https://doi.org/10.4269/ajtmh.17-0563

    Article  PubMed  Google Scholar 

  108. Travi BL, Osorio Y, Melby PC, Chandrasekar B, Arteaga L, Saravia NG (2002) Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp. Infect Immun 70(5):2288–2296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Murback ND, Hans Filho G, Nascimento RA, Nakazato KR, Dorval ME (2011) American cutaneous leishmaniasis: clinical, epidemiological and laboratory studies conducted at a university teaching hospital in Campo Grande, Mato Grosso do Sul, Brazil. An Bras Dermatol 86(1):55–63

    Article  PubMed  Google Scholar 

  110. Mock BA, Nacy CA (1988) Hormonal modulation of sex differences in resistance to Leishmania major systemic infections. Infect Immun 56(12):3316–3319

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Sanchez-Garcia L, Wilkins-Rodriguez A, Salaiza-Suazo N, Morales-Montor J, Becker I. Dihydrotestosterone enhances growth and infectivity of Leishmania Mexicana. Parasite Immunol. 2018;40(3). https://doi.org/10.1111/pim.12512

  112. Qiao Z, Guo Z, Yin G, Yin L, Zhao J, Wunderlich F (1999) Testosterone inhibits apoptosis of Leishmania donovani-infected macrophages. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi = Chinese Journal of Parasitology & Parasitic Diseases 17(1):21–24

    CAS  Google Scholar 

  113. Liu L, Wang L, Zhao Y, Wang Y, Wang Z, Qiao Z (2006) Testosterone attenuates p38 MAPK pathway during Leishmania donovani infection of macrophages. Parasitol Res 99(2):189–193. https://doi.org/10.1007/s00436-006-0168-1

    Article  PubMed  Google Scholar 

  114. Girard LR, Fiedler TJ, Harris TW, Carvalho F, Antoshechkin I, Han M et al (2007) WormBook: the online review of Caenorhabditis elegans biology. Nucleic Acids Res 35:D472–D475. https://doi.org/10.1093/nar/gkl894

    Article  CAS  PubMed  Google Scholar 

  115. Behnke JM, De Clercq D, Sacko M, Gilbert FS, Ouattara DB, Vercruysse J (2000) The epidemiology of human hookworm infections in the southern region of Mali. Trop Med Int Health 5(5):343–354

    Article  CAS  PubMed  Google Scholar 

  116. Moore SL, Wilson K (2002) Parasites as a viability cost of sexual selection in natural populations of mammals. Science (New York, NY) 297(5589):2015–2018. https://doi.org/10.1126/science.1074196

    Article  CAS  Google Scholar 

  117. Poulin R (1996) Sexual inequalities in helminth infections: a cost of being a male? Am Nat 147(2):287–295. https://doi.org/10.1086/285851

    Article  Google Scholar 

  118. Tiuria R, Horii Y, Makimura S, Ishikawa N, Tsuchiya K, Nawa Y (1995) Effect of testosterone on the mucosal defence against intestinal helminths in Indian soft-furred rats, Millardia meltada with reference to goblet and mast cell responses. Parasite Immunol 17(9):479–484

    Article  CAS  PubMed  Google Scholar 

  119. Watanabe K, Hamano S, Noda K, Koga M, Tada I (1999) Strongyloides ratti: additive effect of testosterone implantation and carbon injection on the susceptibility of female mice. Parasitol Res 85(7):522–526

    Article  CAS  PubMed  Google Scholar 

  120. Rivero JC, Inoue Y, Murakami N, Horii Y (2002) Androgen- and estrogen-dependent sex differences in host resistance to Strongyloides venezuelensis infection in Wistar rats. J Vet Med Sci 64(6):457–461

    Article  CAS  PubMed  Google Scholar 

  121. Rivero JC, Inoue Y, Murakami N, Horii Y (2002) Age- and sex-related changes in susceptibility of Wistar rats to Strongyloides venezuelensis infection. J Vet Med Sci 64(6):519–521

    Article  PubMed  Google Scholar 

  122. McRae KM, Stear MJ, Good B, Keane OM (2015) The host immune response to gastrointestinal nematode infection in sheep. Parasite Immunol 37(12):605–613. https://doi.org/10.1111/pim.12290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Hartmann W, Brenz Y, Kingsley MT, Ajonina-Ekoti I, Brattig NW, Liebau E et al (2013) Nematode-derived proteins suppress proliferation and cytokine production of antigen-specific T cells via induction of cell death. PLoS One 8(6):e68380. https://doi.org/10.1371/journal.pone.0068380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Cooper D, Eleftherianos I (2016) Parasitic nematode immunomodulatory strategies: recent advances and perspectives. Pathogens 5(3):58. https://doi.org/10.3390/pathogens5030058

    Article  CAS  PubMed Central  Google Scholar 

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Correspondence to Julie Sellau.

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This article is a contribution to the special issue on Sex differences in immunity – Guest Editors: Hanna Lotter and Marcus Altfeld

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Sellau, J., Groneberg, M. & Lotter, H. Androgen-dependent immune modulation in parasitic infection. Semin Immunopathol 41, 213–224 (2019). https://doi.org/10.1007/s00281-018-0722-9

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