Mumps virus-induced innate immune responses in mouse Sertoli and Leydig cells.

Han Wu,Min Feng,Daishu Han,Qian Jiang,Qihan Li,Lijing Cheng,Lili Shi,Qiaoyuan Chen,Qing Wang,Xiang Zhao

doi:10.1038/srep19507

Han Wu, Min Feng + Show 8 more

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https://doi.org/10.1038/srep19507

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Abstract

Mumps virus (MuV) infection frequently causes orchitis and impairs male fertility. However, the mechanisms underlying the innate immune responses to MuV infection in the testis have yet to be investigated. This study showed that MuV induced innate immune responses in mouse Sertoli and Leydig cells through TLR2 and retinoic acid-inducible gene I (RIG-I) signaling, which result in the production of proinflammatory cytokines and chemokines, including TNF-α, IL-6, MCP-1, CXCL10, and type 1 interferons (IFN-α and IFN-β). By contrast, MuV did not induce the cytokine production in male germ cells. In response to MuV infection, Sertoli cells produced higher levels of proinflammatory cytokines and chemokines but lower levels of type 1 IFNs than Leydig cells did. The MuV-induced cytokine production by Sertoli and Leydig cells was significantly reduced by the knockout of TLR2 or the knockdown of RIG-I signaling. The local injection of MuV into the testis triggered the testicular innate immune responses in vivo. Moreover, MuV infection suppressed testosterone synthesis by Leydig cells. This is the first study examining the innate immune responses to MuV infection in testicular cells. The results provide novel insights into the mechanisms underlying the MuV-induced innate immune responses in the testis.

Highlights

Mumps virus (MuV) infection frequently causes orchitis and impairs male fertility
To examine the innate immune responses of testicular cells to mumps virus (MuV) infection, we analyzed the expression of proinflammatory cytokines, chemokines, and type 1 IFNs in major testicular cell types, including Sertoli, Leydig, and germ cells
Considering that mouse Sertoli and Leydig cells express melanoma differentiation-associated protein 5 (MDA5) and RIG-I16, we examined the roles of MDA5, retinoic acid-inducible gene I (RIG-I), and their signaling adaptor IFN-β promoter stimulator-1 (IPS-1) in MuV-induced innate immune responses by using RNA interference approach

Summary

Introduction

Mumps virus (MuV) infection frequently causes orchitis and impairs male fertility. the mechanisms underlying the innate immune responses to MuV infection in the testis have yet to be investigated. This study showed that MuV induced innate immune responses in mouse Sertoli and Leydig cells through TLR2 and retinoic acid-inducible gene I (RIG-I) signaling, which result in the production of proinflammatory cytokines and chemokines, including TNF-α, IL-6, MCP-1, CXCL10, and type 1 interferons (IFN-α and IFN-β). The MuV-induced cytokine production by Sertoli and Leydig cells was significantly reduced by the knockout of TLR2 or the knockdown of RIG-I signaling. Viral infection triggers the innate immune responses through the activation of some TLRs, RLRs, and cytosolic DNA sensors[9]. RLRs initiate signaling pathway through adaptor IFN-β promoter stimulator-1 (IPS-1), whereas cytosolic DNA sensors use the stimulator of IFN gene[11] These PRR signaling pathways induce the secretion of numerous proinflammatory cytokines, chemokines and type 1 interferons (IFN-α and IFN-β ) through the activation of nuclear factor κ B www.nature.com/scientificreports/. Leydig cells express TLR2, TLR3, TLR4, RIG-I, MDA5 and cytosolic DNA sensor p20415–17

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