RIG-I-like receptors mediate innate antiviral response in mouse testis

Mol Endocrinol. 2013 Sep;27(9):1455-67. doi: 10.1210/me.2013-1075. Epub 2013 Jul 2.


The testis is an immune privileged organ in which the tissue-specific cells have adopted effective innate immune functions against microbial pathogens. Toll-like receptors (TLRs) mediate innate immune response in the testis. The current study demonstrates that melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) initiate the testicular innate antiviral response. Both MDA5 and RIG-I are expressed in Leydig cells, and MDA5 is also expressed in spermatids. Polyinosinic-polycytidylic acid [poly(I:C)], a common agonist of MDA5 and RIG-I, significantly induces the expression of type I interferons (IFN-α/β) and antiviral proteins, including IFN-stimulated gene 15, 2'5'-oligoadenylate synthetase 1, and Mx GTPase 1, in primary TLR3-deficient (TLR3(-/-)) Leydig and germ cells. Moreover, major proinflammatory cytokines, including TNF-α and IL-6, are significantly up-regulated by poly(I:C) in these testicular cells. The poly(I:C)-induced innate antiviral response in the testicular cells is significantly reduced by knockdown of individual MDA5 and RIG-I using specific small interfering RNA. We also provide evidence that local injection of poly(I:C) induces antiviral response in the testis of TLR3(-/-) mice. These data provide novel insights into the mechanisms underlying testicular antiviral response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Immunity, Innate* / drug effects
  • Immunity, Innate* / genetics
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon-Induced Helicase, IFIH1
  • Leydig Cells / drug effects
  • Leydig Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Poly I-C / pharmacology
  • Spermatozoa / drug effects
  • Spermatozoa / metabolism
  • Testis / drug effects
  • Testis / immunology*
  • Testis / virology*


  • Cytokines
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • NF-kappa B
  • Ddx58 protein, mouse
  • Ifih1 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • Poly I-C