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Testicular defense systems: immune privilege and innate immunity

Cellular & Molecular Immunology volume 11, pages 428–437 (2014)Cite this article

Abstract

The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation.

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References

  1. Head JR, Neaves WB, Billingham RE . Immune privilege in the testis. I. Basic parameters of allograft survival. Transplantation 1983; 36: 423–431.

    CAS  PubMed  Google Scholar 

  2. Hedger MP . Immune Privilege of the Testis: Meaning, Mechanisms, and Manifestations. Infection, Immune Homeostasis and Immune Privilege. New York: Springer, 2012: 31–52.

    Google Scholar 

  3. Li N, Wang T, Han D . Structural, cellular and molecular aspects of immune privilege in the testis. Front Immunol 2012; 3: 152.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kaur G, Mital P, Dufour J . Testis immune privilege—assumptions versus facts. Anim Reprod 2013; 10: 3–15.

    CAS  PubMed  Google Scholar 

  5. Weidner W, Krause W . Orchitis. In: Knobil E, Neill JD (ed.) Encyclopedia of Reproduction. San Diego, CA: Academic Press, 1998: 524–527.

    Google Scholar 

  6. Schuppe HC, Meinhardt A, Allam JP, Bergmann M, Weidner W, Haidl G . Chronic orchitis: a neglected cause of male infertility? Andrologia 2008; 40: 84–91.

    PubMed  Google Scholar 

  7. Jacobo P, Guazzone VA, Theas MS, Lustig L . Testicular autoimmunity. Autoimmun Rev 2011; 10: 201–204.

    CAS  PubMed  Google Scholar 

  8. Simpson E . A historical perspective on immunological privilege. Immunol Rev 2006; 213: 12–22.

    PubMed  Google Scholar 

  9. Fijak M, Meinhardt A . The testis in immune privilege. Immunol Rev 2006; 213: 66–81.

    CAS  PubMed  Google Scholar 

  10. Setchell BP . The testis and tissue transplantation: historical aspects. J Reprod Immunol 1990; 18: 1–8.

    CAS  PubMed  Google Scholar 

  11. Sand K . Experiments on the internal secretion of the sexual glands, especially on experimental hermaphroditism. J Physiol 1919; 53: 257–263.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Mital P, Kaur G, Dufour JM . Immunoprotective sertoli cells: making allogeneic and xenogeneic transplantation feasible. Reproduction 2010; 139: 495–504.

    CAS  PubMed  Google Scholar 

  13. Lanza RP, Chick WL . Pancreatic Islet Transplantation: Immunomodulation of Pancreatic Islets. Georgetown, TX: R.G. Landes, 1994.

    Google Scholar 

  14. Tung KS, Teuscher C, Meng AL . Autoimmunity to spermatozoa and the testis. Immunol Rev 1981; 55: 217–255.

    CAS  PubMed  Google Scholar 

  15. Brinster RL, Avarbock MR . Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci USA 1994; 91: 11303–11307.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Silva RC, Costa GM, Lacerda SM, Batlouni SR, Soares JM, Avelar GF et al. Germ cell transplantation in felids: a potential approach to preserving endangered species. J Androl 2012; 33: 264–276.

    PubMed  Google Scholar 

  17. Setchell BP, Granholm T, Ritzen EM . Failure of thyroid allografts to function in the testes of cynomolgous monkeys. J Reprod Immunol 1995; 28: 75–80.

    CAS  PubMed  Google Scholar 

  18. Maddocks S, Setchell BP . The rejection of thyroid allografts in the ovine testis. Immunol Cell Biol 1988; 66( Pt 1): 1–8.

    PubMed  Google Scholar 

  19. Fijak M, Bhushan S, Meinhardt A . Immunoprivileged sites: the testis. Methods Mol Biol 2011; 677: 459–470.

    CAS  PubMed  Google Scholar 

  20. Barker CF, Billingham RE . Immunologically privileged sites. Adv Immunol 1977; 25: 1–54.

    CAS  PubMed  Google Scholar 

  21. Yule TD, Montoya GD, Russell LD, Williams TM, Tung KS . Autoantigenic germ cells exist outside the blood testis barrier. J Immunol 1988; 141: 1161–1167.

    CAS  PubMed  Google Scholar 

  22. Meinhardt A, Hedger MP . Immunological, paracrine and endocrine aspects of testicular immune privilege. Mol Cell Endocrinol 2011; 335: 60–68.

    CAS  PubMed  Google Scholar 

  23. Cheng CY, Mruk DD . The blood–testis barrier and its implications for male contraception. Pharmacol Rev 2012; 64: 16–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Wyatt CR, Law L, Magnuson JA, Griswold MD, Magnuson NS . Suppression of lymphocyte proliferation by proteins secreted by cultured Sertoli cells. J Reprod Immunol 1988; 14: 27–40.

    CAS  PubMed  Google Scholar 

  25. de Cesaris P, Filippini A, Cervelli C, Riccioli A, Muci S, Starace G et al. Immunosuppressive molecules produced by Sertoli cells cultured in vitro: biological effects on lymphocytes. Biochem Biophys Res Commun 1992; 186: 1639–1646.

    CAS  PubMed  Google Scholar 

  26. Sanberg PR, Borlongan CV, Saporta S, Cameron DF . Testis-derived Sertoli cells survive and provide localized immunoprotection for xenografts in rat brain. Nat Biotechnol 1996; 14: 1692–1695.

    CAS  PubMed  Google Scholar 

  27. Suarez-Pinzon W, Korbutt GS, Power R, Hooton J, Rajotte RV, Rabinovitch A . Testicular sertoli cells protect islet beta-cells from autoimmune destruction in NOD mice by a transforming growth factor-beta1-dependent mechanism. Diabetes 2000; 49: 1810–1818.

    CAS  PubMed  Google Scholar 

  28. Nakanishi Y, Shiratsuchi A . Phagocytic removal of apoptotic spermatogenic cells by Sertoli cells: mechanisms and consequences. Biol Pharm Bull 2004; 27: 13–16.

    CAS  PubMed  Google Scholar 

  29. Tanaka M, Asano K, Qiu CH . Immune regulation by apoptotic cell clearance. Ann NY Acad Sci 2010; 1209: 37–42.

    CAS  PubMed  Google Scholar 

  30. Zhang X, Wang T, Deng T, Xiong W, Lui P, Li N et al. Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4. Mol Cell Endocrinol 2013; 365: 162–173.

    CAS  PubMed  Google Scholar 

  31. Haugen TB, Landmark BF, Josefsen GM, Hansson V, Hogset A . The mature form of interleukin-1 alpha is constitutively expressed in immature male germ cells from rat. Mol Cell Endocrinol 1994; 105: R19–R23.

    CAS  PubMed  Google Scholar 

  32. De SK, Chen HL, Pace JL, Hunt JS, Terranova PF, Enders GC . Expression of tumor necrosis factor-alpha in mouse spermatogenic cells. Endocrinology 1993; 133: 389–396.

    CAS  PubMed  Google Scholar 

  33. D'Alessio A, Riccioli A, Lauretti P, Padula F, Muciaccia B, de Cesaris P et al. Testicular FasL is expressed by sperm cells. Proc Natl Acad Sci USA 2001; 98: 3316–3321.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ju ST, Panka DJ, Cui H, Ettinger R, el-Khatib M, Sherr DH et al. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 1995; 373: 444–448.

    CAS  PubMed  Google Scholar 

  35. Hedger MP . Macrophages and the immune responsiveness of the testis. J Reprod Immunol 2002; 57: 19–34.

    CAS  PubMed  Google Scholar 

  36. Hutson JC . Physiologic interactions between macrophages and Leydig cells. Exp Biol Med (Maywood) 2006; 231: 1–7.

    CAS  Google Scholar 

  37. Kern S, Robertson SA, Mau VJ, Maddocks S . Cytokine secretion by macrophages in the rat testis. Biol Reprod 1995; 53: 1407–1416.

    CAS  PubMed  Google Scholar 

  38. Winnall WR, Muir JA, Hedger MP . Rat resident testicular macrophages have an alternatively activated phenotype and constitutively produce interleukin-10 in vitro. J Leukoc Biol 2011; 90: 133–143.

    CAS  PubMed  Google Scholar 

  39. Bhushan S, Hossain H, Lu Y, Geisler A, Tchatalbachev S, Mikulski Z et al. Uropathogenic E. coli induce different immune response in testicular and peritoneal macrophages: implications for testicular immune privilege. PLoS ONE 2011; 6: e28452.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Theas MS, Rival C, Jarazo-Dietrich S, Jacobo P, Guazzone VA, Lustig L . Tumour necrosis factor-alpha released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis. Hum Reprod 2008; 23: 1865–1872.

    CAS  PubMed  Google Scholar 

  41. Rival C, Theas MS, Suescun MO, Jacobo P, Guazzone V, van Rooijen N et al. Functional and phenotypic characteristics of testicular macrophages in experimental autoimmune orchitis. J Pathol 2008; 215: 108–117.

    CAS  PubMed  Google Scholar 

  42. Frungieri MB, Calandra RS, Lustig L, Meineke V, Kohn FM, Vogt HJ et al. Number, distribution pattern, and identification of macrophages in the testes of infertile men. Fertil Steril 2002; 78: 298–306.

    PubMed  Google Scholar 

  43. Rival C, Lustig L, Iosub R, Guazzone VA, Schneider E, Meinhardt A et al. Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis. Cell Tissue Res 2006; 324: 311–318.

    PubMed  Google Scholar 

  44. Banchereau J, Steinman RM . Dendritic cells and the control of immunity. Nature 1998; 392: 245–252.

    CAS  PubMed  Google Scholar 

  45. Rival C, Guazzone VA, von Wulffen W, Hackstein H, Schneider E, Lustig L et al. Expression of co-stimulatory molecules, chemokine receptors and proinflammatory cytokines in dendritic cells from normal and chronically inflamed rat testis. Mol Hum Reprod 2007; 13: 853–861.

    CAS  PubMed  Google Scholar 

  46. Guazzone VA, Hollwegs S, Mardirosian M, Jacobo P, Hackstein H, Wygrecka M et al. Characterization of dendritic cells in testicular draining lymph nodes in a rat model of experimental autoimmune orchitis. Int J Androl 2011; 34: 276–289.

    CAS  PubMed  Google Scholar 

  47. Hedger MP, Meinhardt A . Local regulation of T cell numbers and lymphocyte-inhibiting activity in the interstitial tissue of the adult rat testis. J Reprod Immunol 2000; 48: 69–80.

    CAS  PubMed  Google Scholar 

  48. Lustig L, Lourtau L, Perez R, Doncel GF . Phenotypic characterization of lymphocytic cell infiltrates into the testes of rats undergoing autoimmune orchitis. Int J Androl 1993; 16: 279–284.

    CAS  PubMed  Google Scholar 

  49. el-Demiry MI, Hargreave TB, Busuttil A, Elton R, James K, Chisholm GD . Immunocompetent cells in human testis in health and disease. Fertil Steril 1987; 48: 470–479.

    CAS  PubMed  Google Scholar 

  50. Wheeler K, Tardif S, Rival C, Luu B, Bui E, del Rio R et al. Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy. Proc Natl Acad Sci USA 2011; 108: 7511–7516.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Jacobo P, Guazzone VA, Jarazo-Dietrich S, Theas MS, Lustig L . Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis. J Reprod Immunol 2009; 81: 44–54.

    CAS  PubMed  Google Scholar 

  52. Dai Z, Nasr IW, Reel M, Deng S, Diggs L, Larsen CP et al. Impaired recall of CD8 memory T cells in immunologically privileged tissue. J Immunol 2005; 174: 1165–1170.

    CAS  PubMed  Google Scholar 

  53. Nasr IW, Wang Y, Gao G, Deng S, Diggs L, Rothstein DM et al. Testicular immune privilege promotes transplantation tolerance by altering the balance between memory and regulatory T cells. J Immunol 2005; 174: 6161–6168.

    CAS  PubMed  Google Scholar 

  54. Hussein MR, Abou-Deif ES, Bedaiwy MA, Said TM, Mustafa MG, Nada E et al. Phenotypic characterization of the immune and mast cell infiltrates in the human testis shows normal and abnormal spermatogenesis. Fertil Steril 2005; 83: 1447–1453.

    PubMed  Google Scholar 

  55. Iosub R, Klug J, Fijak M, Schneider E, Frohlich S, Blumbach K et al. Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2. J Pathol 2006; 208: 686–698.

    CAS  PubMed  Google Scholar 

  56. Abe M, Kurosawa M, Ishikawa O, Miyachi Y, Kido H . Mast cell tryptase stimulates both human dermal fibroblast proliferation and type I collagen production. Clin Exp Allergy 1998; 28: 1509–1517.

    CAS  PubMed  Google Scholar 

  57. Apa DD, Cayan S, Polat A, Akbay E . Mast cells and fibrosis on testicular biopsies in male infertility. Arch Androl 2002; 48: 337–344.

    CAS  PubMed  Google Scholar 

  58. Lu LF, Lind EF, Gondek DC, Bennett KA, Gleeson MW, Pino-Lagos K et al. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 2006; 442: 997–1002.

    CAS  PubMed  Google Scholar 

  59. Diemer T, Hales DB, Weidner W . Immune-endocrine interactions and Leydig cell function: the role of cytokines. Andrologia 2003; 35: 55–63.

    CAS  PubMed  Google Scholar 

  60. Dejucq N, Lienard MO, Guillaume E, Dorval I, Jegou B . Expression of interferons-alpha and -gamma in testicular interstitial tissue and spermatogonia of the rat. Endocrinology 1998; 139: 3081–3087.

    CAS  PubMed  Google Scholar 

  61. Melaine N, Lienard MO, Guillaume E, Ruffault A, Dejucq-Rainsford N, Jegou B . Production of the antiviral proteins 2′5′oligoadenylate synthetase, PKR and Mx in interstitial cells and spermatogonia. J Reprod Immunol 2003; 59: 53–60.

    CAS  PubMed  Google Scholar 

  62. Le Tortorec A, Denis H, Satie AP, Patard JJ, Ruffault A, Jegou B et al. Antiviral responses of human Leydig cells to mumps virus infection or poly I:C stimulation. Hum Reprod 2008; 23: 2095–2103.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Raburn DJ, Coquelin A, Reinhart AJ, Hutson JC . Regulation of the macrophage population in postnatal rat testis. J Reprod Immunol 1993; 24: 139–151.

    CAS  PubMed  Google Scholar 

  64. De Carolis S, Botta A, Fatigante G, Garofalo S, Ferrazzani S, Gasbarrini A et al. Celiac disease and inflammatory bowel disease in pregnancy. Lupus 2004; 13: 653–658.

    CAS  PubMed  Google Scholar 

  65. Meng J, Greenlee AR, Taub CJ, Braun RE . Sertoli cell-specific deletion of the androgen receptor compromises testicular immune privilege in mice. Biol Reprod 2011; 85: 254–260.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Fijak M, Schneider E, Klug J, Bhushan S, Hackstein H, Schuler G et al. 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 2011; 186: 5162–5172.

    CAS  PubMed  Google Scholar 

  67. Maekawa M, Kamimura K, Nagano T . Peritubular myoid cells in the testis: their structure and function. Arch Histol Cytol 1996; 59: 1–13.

    CAS  PubMed  Google Scholar 

  68. Mayerhofer A . Human testicular peritubular cells: more than meets the eye. Reproduction 2013; 145: R107–R116.

    CAS  PubMed  Google Scholar 

  69. Cutolo M . Androgens in rheumatoid arthritis: when are they effectors? Arthritis Res Ther 2009; 11: 126.

    PubMed  PubMed Central  Google Scholar 

  70. Page ST, Plymate SR, Bremner WJ, Matsumoto AM, Hess DL, Lin DW et al. Effect of medical castration on CD4+ CD25+ T cells, CD8+ T cell IFN-gamma expression, and NK cells: a physiological role for testosterone and/or its metabolites. Am J Physiol Endocrinol Metab 2006; 290: E856–E863.

    CAS  PubMed  Google Scholar 

  71. Meng J, Holdcraft RW, Shima JE, Griswold MD, Braun RE . Androgens regulate the permeability of the blood–testis barrier. Proc Natl Acad Sci USA 2005; 102: 16696–16700.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Dhein J, Walczak H, Baumler C, Debatin KM, Krammer PH . Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 1995; 373: 438–441.

    CAS  PubMed  Google Scholar 

  73. Suda T, Takahashi T, Golstein P, Nagata S . Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 1993; 75: 1169–1178.

    CAS  PubMed  Google Scholar 

  74. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC . A role for CD95 ligand in preventing graft rejection. Nature 1995; 377: 630–632.

    CAS  PubMed  Google Scholar 

  75. Korbutt GS, Suarez-Pinzon WL, Power RF, Rajotte RV, Rabinovitch A . Testicular Sertoli cells exert both protective and destructive effects on syngeneic islet grafts in non-obese diabetic mice. Diabetologia 2000; 43: 474–480.

    CAS  PubMed  Google Scholar 

  76. Keir ME, Butte MJ, Freeman GJ, Sharpe AH . PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26: 677–704.

    CAS  PubMed  Google Scholar 

  77. Cheng X, Dai H, Wan N, Moore Y, Vankayalapati R, Dai Z . Interaction of programmed death-1 and programmed death-1 ligand-1 contributes to testicular immune privilege. Transplantation 2009; 87: 1778–1786.

    CAS  PubMed  Google Scholar 

  78. Lemke G, Rothlin CV . Immunobiology of the TAM receptors. Nat Rev Immunol 2008; 8: 327–336.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Wang H, Chen Y, Ge Y, Ma P, Ma Q, Ma J et al. Immunoexpression of Tyro 3 family receptors—Tyro 3, Axl, and Mer—and their ligand Gas6 in postnatal developing mouse testis. J Histochem Cytochem 2005; 53: 1355–1364.

    CAS  PubMed  Google Scholar 

  80. Lu Q, Gore M, Zhang Q, Camenisch T, Boast S, Casagranda F et al. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature 1999; 398: 723–728.

    CAS  PubMed  Google Scholar 

  81. Chen Y, Wang H, Qi N, Wu H, Xiong W, Ma J et al. Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice. Reproduction 2009; 138: 655–666.

    CAS  PubMed  Google Scholar 

  82. Zhang Y, Li N, Chen Q, Yan K, Liu Z, Zhang X et al. Breakdown of immune homeostasis in the testis of mice lacking Tyro3, Axl and Mer receptor tyrosine kinases. Immunol Cell Biol 2013; 91: 416–426.

    CAS  PubMed  Google Scholar 

  83. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G . TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 2007; 131: 1124–1136.

    CAS  PubMed  Google Scholar 

  84. Sun B, Qi N, Shang T, Wu H, Deng T, Han D . Sertoli cell-initiated testicular innate immune response through Toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors. Endocrinology 2010; 151: 2886–2897.

    CAS  PubMed  Google Scholar 

  85. Shang T, Zhang X, Wang T, Sun B, Deng T, Han D . Toll-like receptor-initiated testicular innate immune responses in mouse Leydig cells. Endocrinology 2011; 152: 2827–2836.

    CAS  PubMed  Google Scholar 

  86. Xiong W, Chen Y, Wang H, Wang H, Wu H, Lu Q et al. Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction 2008; 135: 77–87.

    CAS  PubMed  Google Scholar 

  87. Mullaney BP, Skinner MK . Transforming growth factor-beta (beta 1, beta 2, and beta 3) gene expression and action during pubertal development of the seminiferous tubule: potential role at the onset of spermatogenesis. Mol Endocrinol 1993; 7: 67–76.

    CAS  PubMed  Google Scholar 

  88. Avallet O, Vigier M, Leduque P, Dubois PM, Saez JM . Expression and regulation of transforming growth factor-beta 1 messenger ribonucleic acid and protein in cultured porcine Leydig and Sertoli cells. Endocrinology 1994; 134: 2079–2087.

    CAS  PubMed  Google Scholar 

  89. Buzzard JJ, Loveland KL, O'Bryan MK, O'Connor AE, Bakker M, Hayashi T et al. Changes in circulating and testicular levels of inhibin A and B and activin A during postnatal development in the rat. Endocrinology 2004; 145: 3532–3541.

    CAS  PubMed  Google Scholar 

  90. Barakat B, O'Connor AE, Gold E, de Kretser DM, Loveland KL . Inhibin, activin, follistatin and FSH serum levels and testicular production are highly modulated during the first spermatogenic wave in mice. Reproduction 2008; 136: 345–359.

    CAS  PubMed  Google Scholar 

  91. Meehan T, Schlatt S, O'Bryan MK, de Kretser DM, Loveland KL . Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH. Dev Biol 2000; 220: 225–237.

    CAS  PubMed  Google Scholar 

  92. Phillips DJ, de Kretser DM, Hedger MP . Activin and related proteins in inflammation: not just interested bystanders. Cytokine Growth Factor Rev 2009; 20: 153–164.

    CAS  PubMed  Google Scholar 

  93. O'Bryan MK, Gerdprasert O, Nikolic-Paterson DJ, Meinhardt A, Muir JA, Foulds LM et al. Cytokine profiles in the testes of rats treated with lipopolysaccharide reveal localized suppression of inflammatory responses. Am J Physiol Regul Integr Comp Physiol 2005; 288: R1744–R1755.

    CAS  PubMed  Google Scholar 

  94. Watanabe M, Kashiwakura Y, Kusumi N, Tamayose K, Nasu Y, Nagai A et al. Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis. Gene Ther 2005; 12: 1126–1132.

    CAS  PubMed  Google Scholar 

  95. Dejucq N, Dugast I, Ruffault A, van der Meide PH, Jegou B . Interferon-alpha and -gamma expression in the rat testis. Endocrinology 1995; 136: 4925–4931.

    CAS  PubMed  Google Scholar 

  96. Dejucq N, Chousterman S, Jegou B . The testicular antiviral defense system: localization, expression, and regulation of 2′5′ oligoadenylate synthetase, double-stranded RNA-activated protein kinase, and Mx proteins in the rat seminiferous tubule. J Cell Biol 1997; 139: 865–873.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Com E, Bourgeon F, Evrard B, Ganz T, Colleu D, Jegou B et al. Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans. Biol Reprod 2003; 68: 95–104.

    CAS  PubMed  Google Scholar 

  98. Iwasaki A, Medzhitov R . Regulation of adaptive immunity by the innate immune system. Science 2010; 327: 291–295.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Carta S, Castellani P, Delfino L, Tassi S, Vene R, Rubartelli A . DAMPs and inflammatory processes: the role of redox in the different outcomes. J Leukoc Biol 2009; 86: 549–555.

    CAS  PubMed  Google Scholar 

  100. Kumar H, Kawai T, Akira S . Pathogen recognition by the innate immune system. Int Rev Immunol 2011; 30: 16–34.

    CAS  PubMed  Google Scholar 

  101. Keating SE, Baran M, Bowie AG . Cytosolic DNA sensors regulating type I interferon induction. Trends Immunol 2011; 32: 574–581.

    CAS  PubMed  Google Scholar 

  102. Riccioli A, Starace D, Galli R, Fuso A, Scarpa S, Palombi F et al. Sertoli cells initiate testicular innate immune responses through TLR activation. J Immunol 2006; 177: 7122–7130.

    CAS  PubMed  Google Scholar 

  103. Hedger MP . Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation—a perspective. J Reprod Immunol 2011; 88: 130–141.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Palladino MA, Johnson TA, Gupta R, Chapman JL, Ojha P . Members of the Toll-like receptor family of innate immunity pattern-recognition receptors are abundant in the male rat reproductive tract. Biol Reprod 2007; 76: 958–964.

    CAS  PubMed  Google Scholar 

  105. Bhushan S, Tchatalbachev S, Klug J, Fijak M, Pineau C, Chakraborty T et al. Uropathogenic Escherichia coli block MyD88-dependent and activate MyD88-independent signaling pathways in rat testicular cells. J Immunol 2008; 180: 5537–5547.

    CAS  PubMed  Google Scholar 

  106. Wu H, Wang H, Xiong W, Chen S, Tang H, Han D . Expression patterns and functions of toll-like receptors in mouse Sertoli cells. Endocrinology 2008; 149: 4402–4412.

    CAS  PubMed  Google Scholar 

  107. Starace D, Galli R, Paone A, de Cesaris P, Filippini A, Ziparo E et al. Toll-like receptor 3 activation induces antiviral immune responses in mouse Sertoli cells. Biol Reprod 2008; 79: 766–775.

    CAS  PubMed  Google Scholar 

  108. Wang T, Zhang X, Chen Q, Deng T, Zhang Y, Li N et al. Toll-like receptor 3-initiated antiviral responses in mouse male germ cells in vitro. Biol Reprod 2012; 86: 106.

    PubMed  Google Scholar 

  109. Chen Q, Zhu W, Liu Z, Yan K, Zhao S, Han D . Toll-like receptor 11-initiated innate immune response in male mouse germ cells. Biol Reprod 2014; 90: 308.

    Google Scholar 

  110. Loo YM, Gale M Jr . Immune signaling by RIG-I-like receptors. Immunity 2011; 34: 680–692.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 2005; 175: 2851–2858.

    CAS  PubMed  Google Scholar 

  112. Zhu W, Chen Q, Yan K, Liu Z, Li N, Zhang X et al. RIG-I-like receptors mediate innate antiviral response in mouse testis. Mol Endocrinol 2013; 27: 1455–1467.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Kanneganti TD, Lamkanfi M, Nunez G . Intracellular NOD-like receptors in host defense and disease. Immunity 2007; 27: 549–559.

    CAS  PubMed  Google Scholar 

  114. Strowig T, Henao-Mejia J, Elinav E, Flavell R . Inflammasomes in health and disease. Nature 2012; 481: 278–286.

    CAS  PubMed  Google Scholar 

  115. Lupfer C, Kanneganti TD . The expanding role of NLRs in antiviral immunity. Immunol Rev 2013; 255: 13–24.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grants: 31171445, 31261160491 and 31371518).

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  1. Shutao Zhao and Weiwei Zhu: These authors contributed equally to the work.

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  1. Department of Cell Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Shutao Zhao, Weiwei Zhu, Shepu Xue & Daishu Han

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Zhao, S., Zhu, W., Xue, S. et al. Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol 11, 428–437 (2014). https://doi.org/10.1038/cmi.2014.38

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  • DOI: https://doi.org/10.1038/cmi.2014.38

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