Commensal-derived trehalose monocorynomycolate triggers γδ T cell-driven protective ocular barrier immunity

Area of Science:

• Microbiology
• Immunology
• Microbial Therapeutics

Background:

• Commensal microbes interact with host receptors, influencing host physiology.
• Understanding microbial factors that modulate host immunity is crucial for homeostasis and therapeutic development.

Purpose of the Study:

• To identify specific microbial factors from commensals that stimulate host immune responses.
• To investigate the therapeutic potential of identified microbial factors in enhancing immunity at barrier sites.

Main Methods:

• Identification and isolation of trehalose monocorynomycolate (TMCM) from Corynebacterium mastitidis.
• Assessment of TMCM's effect on interleukin-17 (IL-17) production by Vγ4 γδ T cells.
• Analysis of the signaling pathways involved (IL-1R, γδ T cell receptor).
• Evaluation of synthetic TMCM's efficacy in vivo for protection against bacterial infection.

Main Results:

• TMCM was identified as a potent stimulator of IL-17 production by ocular surface Vγ4 γδ T cells.
• TMCM-induced IL-17 responses were dependent on IL-1R and γδ T cell receptor (TCR) signaling.
• Synthetic TMCM conferred protective immunity against bacterial infection at the ocular surface, as well as in draining tissues and skin.
• TCR engagement enhanced IL-1R1 expression on γδ T cells.

Conclusions:

• TMCM is a key mediator of commensal-driven immune defense at barrier sites.
• TMCM demonstrates therapeutic potential for strengthening IL-17-mediated protection against infections.