<p>Subject demographics.</p>

Among them, CXCL10 was the most sensitive and strongly induced gene, displaying rapid upregulation even at low IFNγ concentrations. Notably, keratinocytes from individuals with asymptomatic HSV-2 infection exhibited significantly greater IFNγ responses at both the mRNA and protein levels compared with those from symptomatic donors, particularly at physiologically low IFNγ doses. This heightened responsiveness was associated with increased nuclear localization of phosphorylated STAT1 following IFNγ stimulation, despite similar baseline expression of IFNγ receptor and STAT1 across donor groups.

While IFNγ pretreatment similarly inhibited HSV replication in keratinocytes from both cohorts, the enhanced chemokine production by keratinocytes from asymptomatic individuals may promote more efficient recruitment of antiviral immune cells. Together, these findings identify intrinsic variation in epithelial IFNγ signaling as a potential host factor associated with clinical outcomes in HSV infection. The results suggest that CXCL10-mediated immune recruitment might be a key mechanism linking tissue-resident T cell cytokine signaling to epithelial antiviral defense.

Understanding variability in epithelial barrier immune defense may be crucial to improving therapies and vaccine strategies for genital herpes infection.</p></div>