Microbe-derived trehalose-conjugated corynomycolates stimulate gdT cells and protect the eye from pathogenic infection
Commensals are key players in host physiology through crosstalk between commensal-derived molecules and host receptors. Identification of microbe-specific molecules that causally affect host physiology is critical for deciphering the establishment of homeostasis at the host/microbe interface and for understanding how immunity is shaped by microbial-based therapeutics. Here, we identify one component of Corynebacterium mastitidis (C. mast) - trehalose monocorynomycolate (TMCM) - that stimulates interleukin (IL)-17 from gdT cells at the ocular surface. Mechanistically, TMCM-mediated IL-17 responses largely depend on IL-1 signaling and stimulation of the gdT cell receptor. Application of synthetic TMCM alone protects mice against pathogenic corneal infection. Collectively, our study identifies TMCM as a stimulant of gdT cells and demonstrates its potential as a gdT cell adjuvant and a therapeutic to enhance protective immunity at sites seeded with gdT cells like the ocular surface.