Toll-Like Receptor 3-Initiated Antiviral Responses in Mouse Male Germ Cells In Vitro1

Abstract

The testis is an immunoprivileged site where local cell-initiated innate immunity plays a crucial role in antimicrobial responses. Toll-like receptors (TLRs) mediate innate immune responses in testicular somatic cells. Although several TLRs are expressed in some stages of male germ cells, the potential role of TLRs in triggering antimicrobial responses in the germ cells has yet to be exclusively studied. The current study demonstrates that TLR3 is constitutively expressed in spermatogonia and spermatocytes and can be activated by a synthetic double-strained RNA analog, polyinosinic-polycytidylic acid. TLR3 activation in these male germ cells up-regulates the expression of proinflammatory cytokines, such as interleukin IL1B, IL6, and tumor necrosis factor alpha, through activation of nuclear factor kappa B; it also induces production of type 1 interferons (IFNA and IFNB) through the activation of IFN regulatory factor 3. In addition, TLR3 activation increases the production of two major antiviral proteins, namely, double-stranded RNA-activated protein kinase and MX1 protein, by germ cells. Data in this article describe an antiviral response of male germ cells through the activation of TLR3 in vitro.

Testicular defense systems: immune privilege and innate immunity

“…105 We recently demonstrated that TLR3 in spermatogonia and spermatocytes and TLR11 in spermatids initiate innate immune responses. 108,109 The TLR-initiated innate immune responses in male germ cells are particularly interesting because the germ cells represent a majority of the testicular cell population. Moreover, the adluminal compartments of the seminiferous tubules are separated from the interstitial immune components by the BTB.…”

Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4

“…Mouse Sertoli cells express TLR2 to TLR5, which can be activated by their respective PAMPs (Riccioli et al, 2006;Starace et al, 2008;Sun et al, 2010;Winnall et al, 2011;Wu et al, 2008). Expression, as well as activation, of TLR3 and TLR4 in mouse Leydig cells, and TLR3 in male germ cells were recently demonstrated (Shang et al, 2011;Wang et al, 2012). These studies have suggested that TLRs in the testicular cells play a role for the testis to mount appropriate local responses to invading microbial antigens.…”

Gestational form of Selenium in Free-Choice Mineral Mixes Affects Transcriptome Profiles of the Neonatal Calf Testis, Including those of Steroidogenic and Spermatogenic Pathways

“…Collectively, these MIXinduced changes in mRNA content suggest biochemical changes that could decrease the systemic androgen/estrogen ratio. Although not found by RT-PCR analysis, microarray analysis indicated that the expression of mRNA for TLR3 was also decreased in the testis of calves born to MIXsupplemented dams, which would further exacerbate an androgen to estrogen shift, as activation of the TLR3 receptor is responsible for triggering the testicular innate immune response, decreasing circulating concentrations of testosterone [44,45]. Although speculative, increased expression of mRNA for CDK5R1 in the testis of calves born to MIXdams may reflect a compensatory mechanism to maintain the testis ability to produce sufficient testosterone.…”