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

ABSTRACT: 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 found an unexpected protective role of obesity against herpes simplex virus 2 infection of the genital mucosa in mice. Although conventional antiviral immunity was comparable between obese mice and lean mice, obesity enhanced the cytotoxic subset of γδ T cells. This effect was mediated by L-arginine produced by commensal microbiota in the genital mucosa, which induced “pseudonormoxia” of γδ T cells, resulting in increased NKG2D expression of γδ T cells through the downregulation of HIF1A by inducing 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE201274 | GEO | 2023/07/12

REPOSITORIES: GEO

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

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

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