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

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

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School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005 China.


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.

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