{"paper_id":"423af5bb-3ed6-47b4-9317-005eff9b5fff","body_text":"SUMMARY\nCommensals shape host physiology through molecular crosstalk with host receptors. Identifying specific microbial factors that causally influence host immunity is key to understanding homeostasis at the host-microbe interface and advancing microbial-based therapeutics. Here, we identify trehalose monocorynomycolate (TMCM) from Corynebacterium mastitidis (C. mast) as a potent stimulator of IL-17 production by γδ T cells at the ocular surface. Mechanistically, TMCM-driven IL-17 responses require both IL-1 signals and γδ TCR signaling, which also supports endogenous γδ T cell IL-1R1 expression. Notably, synthetic TMCM alone is sufficient to mimic the effect of C. mast in inducing γδ T cell immunity and protect against pathogenic corneal infection. Our findings establish TMCM as a key mediator of commensal-driven immune defense, highlighting its potential as a γδ T cell adjuvant and a microbiome-informed therapeutic to enhance IL-17-driven protection at barrier sites such as the ocular surface.\nHIGHLIGHTS\nCorynomycolates enable ocular C. mast colonization and protective IL-17 immunity\nTMCM drives IL-17 from γδ T cells through TCR and IL-1R signaling\nγδ TCR signaling maintains the expression of endogenous IL-1R1\nSynthetic TMCM mimics the ability of C. mast to induce γδ T cell immunity in the eye\nTMCM protects against P. aeruginosa keratitis, highlighting its therapeutic potential\nCompeting Interest Statement\nRRC, XX and BS: patent application \"CORYNEBACTERIUM MASTITIDIS-DERIVED MYCOLATES FOR TREATING OCULAR SURFACE DISEASES\" No. 63/642,512 filed May 3, 2024. HHS Reference: E‑126-2024-0-US-01","source_license":"Public-Domain","license_restricted":false}