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Shane, J.

Publications and source records attributed to Shane, J..

2 recordsLinked to original sources

Defining the Functional Consequence of the Human Ocular Microbiome

The ocular surface is one of the body's most environmentally exposed mucosal barriers, yet it is considered low biomass and harbors orders of magnitude fewer bacteria than microbe-rich sites like the gut. This has cast doubt on whether a functional core ocular microbiome exists at all. Having previously defined a protective gd T cell and IL-17 axis engaged by the murine commensal Corynebacterium mastitidis, we asked whether human-derived bacteria could do the same. Pairing sequencing and culturomics of healthy human conjunctiva from two geographically distinct cohorts, we define a stable core microbiome and identify Corynebacterium bovis as a consistent eye-resident commensal rather than a transient contaminant. In humans, C. bovis elicits a non-pathogenic response marked by IL-17 secretion by {gamma}{delta} T cells and circulating C. bovis-specific IgG, which suggests commensalism rather than pathology. Colonizing mice with human C. bovis strains from Pittsburgh or Miami reproduced this program and conferred protection against ocular infection with Staphylococcus aureus. Together, these findings identify C. bovis as a human-derived ocular commensal that can drive protective {gamma}{delta} T cell immunity, translating a mechanism previously defined only in mice into human relevance and a rational target against sight-threatening infection.

immunology↗

Commensal-derived Trehalose Monocorynomycolate Triggers γδ T Cell-driven Protective Ocular Barrier Immunity

Commensals 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 {gamma}{delta} T cells at the ocular surface. Mechanistically, TMCM-driven IL-17 responses require both IL-1 signals and {gamma}{delta} TCR signaling, which also supports endogenous {gamma}{delta} T cell IL-1R1 expression. Notably, synthetic TMCM alone is sufficient to mimic the effect of C. mast in inducing {gamma}{delta} 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 {gamma}{delta} T cell adjuvant and a microbiome-informed therapeutic to enhance IL-17-driven protection at barrier sites such as the ocular surface. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/643820v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@63139forg.highwire.dtl.DTLVardef@9d6978org.highwire.dtl.DTLVardef@775e37org.highwire.dtl.DTLVardef@ca84b6_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LICorynomycolates enable ocular C. mast colonization and protective IL-17 immunity C_LIO_LITMCM drives IL-17 from {gamma}{delta} T cells through TCR and IL-1R signaling C_LIO_LI{gamma}{delta} TCR signaling maintains the expression of endogenous IL-1R1 C_LIO_LISynthetic TMCM mimics the ability of C. mast to induce {gamma}{delta} T cell immunity in the eye C_LIO_LITMCM protects against P. aeruginosa keratitis, highlighting its therapeutic potential C_LI

immunology↗