Gut-derived vaginal microbiota protects female reproductive organ from viral infection through pseudonormoxia of immune cells

Abstract

Abstract The detrimental role of obesity in various diseases, including metabolic, cardiovascular, autoimmune, infectious, and cancerous diseases, has been known for many years. Conversely, a phenomenon wherein obesity exerts a positive effect in certain conditions has recently been discovered, and this is known as the obesity paradox. However, the obesity paradox remains controversial, and the underlying mechanisms are still not clear. In particular, a possible role for obesity in response to viral infection has not been fully elucidated. In this study, we investigated a case of the obesity paradox in vaginal herpes simplex virus 2 (HSV-2) infection and uncovered the mechanisms whereby obesity protects from vaginal HSV-2 infection by inducing vaginal dysbiosis. Critically, these obesity-related vaginal microbiota produce L-arginine, which promotes γδ T cell immunity that enhances early protection against HSV-2 infection. This study reveals that obesity-induced translocation of gut microbiota to vagina potentiates anti-HSV-2 immunity via reprogramming of γδ T cell metabolism which provides novel insight for development of anti-HSV-2 drugs and understanding the role of microbiota, antiviral γδ T cell immunity, and mechanisms of obesity paradox. Supported by the National Research Foundation of Korea grant NRF-2019R1A2C208749013