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

Abstract

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 differentiationassociated 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. © 2013 by The Endocrine Society.