Obesity enhances antiviral immunity in the genital mucosa through a microbiota-mediated effect on γδ T cells

Obesity is detrimental to the immune system. It impairs lymphatics, T cell 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 gamma delta T cells. This effect is mediated by L-arginine produced by commensal microbiota in the genital mucosa, which induces pseudonormoxia'' of gamma delta T cells, resulting in increased natural killer (NK) group 2 D (NKG2D) expression of gamma delta T cells 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.

Automated summary

Obesity has been found to have detrimental effects on the immune system, but its impact on viral infections has not been well studied. This research shows that obesity can actually offer protective effects against herpes simplex virus 2 infection in the genital mucosa of mice. The study reveals that obesity enhances the cytotoxic subset of gamma delta T cells through L-arginine produced by commensal microbiota, resulting in increased natural killer (NK) group 2 D (NKG2D) expression and protecting mice from lethal genital herpes.