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

Area of Science:

• Microbiology
• Immunology
• Ocular Surface Research

Background:

• Commensal microbes significantly influence host physiology via molecular interactions.
• Understanding microbial factors that modulate host immunity is crucial for maintaining homeostasis and developing microbial therapeutics.

Purpose of the Study:

• To identify specific microbial factors from commensals that stimulate host immune responses.
• To investigate the role of these factors in ocular surface immunity and host defense.

Main Methods:

• Identification and isolation of trehalose monocorynomycolate (TMCM) from *Corynebacterium mastitidis*.
• Assessing TMCM's effect on IL-17 production by γδ T cells in vitro and in vivo.
• Investigating the signaling pathways involved in TMCM-mediated immune stimulation.

Main Results:

• Trehalose monocorynomycolate (TMCM) from *C. mastitidis* was identified as a potent stimulator of IL-17 production by ocular surface γδ T cells.
• TMCM-induced IL-17 responses depend on IL-1 and γδ T cell receptor (TCR) signaling.
• Synthetic TMCM effectively mimicked *C. mastitidis* effects, enhancing γδ T cell immunity and protecting against corneal infection.

Conclusions:

• TMCM is a key mediator of commensal-induced immune defense at the ocular surface.
• TMCM shows potential as a γδ T cell adjuvant and a microbiome-informed therapeutic for enhancing IL-17-driven protection at barrier sites.