Indira Rao (Mentor: Yasmine Belkaid, PhD)

“Skin S. aureus colonization-induced Vg6+ gdT17 cells modulate metabolic and cognitive homeostasis”

Indira Rao, Michel Enamorado-Escalona, Inta Gribonika, Verena Link and Yasmine Belkaid.

The skin, the largest and outermost organ, is uniquely adapted to promote host fitness while tolerating persistence of commensal microbes. While a predominant skin commensal in 30% of the global population, Staphylococcus aureus is also a furtive pathobiont that poses a major public health threat due to the high transmission risk, infection recurrence rate, role in polymicrobial infections and the astonishing propensity for antibiotic resistance. However, despite the occurrence of endogenous infections in 80% of S. aureus carriers, skin response to asymptomatic S. aureus colonization prior to infection remains largely unknown. We find that skin colonization with S. aureus promotes a significant increase in accumulation of IL-17A+ T cells, without inducing skin inflammation. Most of these are innate-like dermal Vg6+ gdT17 cells. Our data also show that dermal gdT17 cells in S. aureus-colonized mice form large & highly motile clusters one week after S. aureus exposure. Mice specifically lacking Vg6+ gdT17 cells (Vg6+ KO) were generated in the lab and do not show significant differences in skin staphylococcal colonization burden. Thus, we observe that Vg6+ gdT17 cells do not serve an immunoregulatory role in anti-staphylococcal immunity. Intrigued by recent reports implicating Vg6+ gdT17 cells in thermogenesis and cognitive function, we surveyed adipose tissues and the brain meninges. Indeed, we find that skin colonization with S. aureus promotes significant Vg6+ gdT17 cell accumulation both in white adipose depots and the brain meninges. Thus, we hypothesize that skin S. aureus colonization-induced increase in adipose and meningeal Vg6+ gdT17 cell accumulation mediates host metabolic and cognitive homeostasis. To test this hypothesis, Vg6-deficient and WT control mice will be tested for metabolic and cognitive fitness. This work will pave the way for mechanistic studies into how S. aureus colonization-induced innate-like Vg6+ gdT17 cells serve non-canonical functions to broadly modulate organismal homeostasis.