Antiviral responses of human Leydig cells to mumps virus infection or poly I:C stimulation

Abstract

BACKGROUNDThe immuno-privileged status of the testis is essential to the maintenance of its functions, and innate immunity is likely to play a key role in limiting harmful viral infections, as demonstrated in the rat. In men mumps virus infects Leydig cells and has deleterious effects on testosterone production and spermatogenesis. The aim of this study was to test whether mumps virus infection of isolated human Leydig cells was associated with an inhibition of their innate antiviral defences.METHODSLeydig cell production of mRNA and protein for interferons (IFNs) and of three antiviral proteins—2′5′ oligoadenylate synthetase (2′5′OAS), double-stranded RNA-activated protein kinase (PKR) and MxA—was investigated, in the absence or presence of mumps virus or viral stimuli including poly I:C, a mimetic of RNA viruses replication product.RESULTSStimulated or not, human Leydig cells appeared unable to produce routinely detectable IFNs α, β and γ. Although the level of PKR remained unchanged after stimulation, the expression of 2′5′OAS and MxA was enhanced following either mumps virus or poly I:C exposure (P < 0.05 versus control).CONCLUSIONSOverall, our results demonstrate that mumps virus replication in human Leydig cells is not associated with a specific inhibition of IFNs or 2′5′OAS, MxA and PKR production and that these cells display relatively weak endogenous antiviral abilities, as opposed to their rat counterparts.

Testicular defense systems: immune privilege and innate immunity

“…The testicular innate antiviral responses have been previously demonstrated based on a series of pioneering studies on the expression and regulation of both interferons (IFNs) and antiviral proteins in the testis by Professor Jégou's group. [60][61][62]95,96 These investigators also showed that several defensins are expressed in murine and human testes, and may contribute to the innate antimicrobial defense. 97 Recent studies have revealed that various PRRs are abundantly expressed in testicular cells and initiate testicular innate immune responses.…”

“…60,61 Human Leydig cells show relatively weak antiviral activity compared with rat cells. 62 These observations raise an interesting question whether the human testis has a weaker innate defense system against viral infection compared with the murine testis. Notably, microbial infection frequently results in orchitis in humans.…”

Genital Tract Sequestration of SIV following Acute Infection

“…It has been suggested that this compartmentalization may be a consequence of differences between the male genital tract and peripheral tissues in both immunological and target cell properties [14], [15], [20], [21], [22], [23], [24], [25], [26], [27], [28]. Histopathologic studies of genital tissues from SIV-infected monkeys have confirmed that infection can occur at these sites [24], [29].…”

In VitroSensitivity of Human Metapneumovirus to Type I Interferons

“…However, no specific association was found between the expression of MxA or PKR mRNAs and the different antiviral activities of the type I IFNs against hMPV. Although the protein levels of MxA and PKR were not measured, and taking into consideration that in several studies researchers found a correlation between mRNA-levels and protein changes (8,11,13,15), these data suggest that these two proteins are not responsible for the differing antiviral activities displayed in these cells by the different type I IFNs.…”