Abstract
Obesity is detrimental to the immune system. It impairs lymphatics, Tcell development, and lymphopoiesis; induces dysfunction of antitumor immunity; and also promotes tumor progression. However, direct evidence of the impact of obesity on viral infection is lacking. We report a protective role of obesity against herpes simplex virus 2 infection of the genital mucosa in mice. Although conventional antiviral immunity is comparable between obese mice and lean mice, obesity enhances the cytotoxic subset of γδ Tcells. This effect is mediated by L-arginine produced by commensal microbiota in the genital mucosa, which induces "pseudonormoxia" of γδ Tcells, resulting in increased natural killer (NK) group 2 D (NKG2D) expression of γδ Tcells through the downregulation of hypoxia-inducible factor 1-alpha (HIF1A) by inducing nitric oxide (NO) production, thereby protecting mice from lethal genital herpes. Thus, our work illuminates one mechanism by which obesity-induced compositional changes in the vaginal microbiota can affect mucosal immune responses against viral infection.
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