Triggering Receptors Expressed on Myeloid Cells 2 Promotes Corneal Resistance Against Pseudomonas aeruginosa by Inhibiting Caspase-1-Dependent Pyroptosis.

Triggering receptors expressed on myeloid cells 2 (TREM2) is a novel cell surface receptor and functions as an immunomodulatory receptor in infectious diseases. In this study, we investigated the function and regulatory mechanism of TREM2 in Pseudomonas aeruginosa ( P. aeruginosa ) keratitis. We found that P. aeruginosa keratitis was more severe in Trem2 -/- versus wild type C57BL/6 mice as indicated by the increased clinical scores, bacterial load, and cornea pathology. The exacerbated disease progression caused by TREM2 deficiency was associated with boosted activation of caspase-1 and subsequent pyroptosis as well as increased expression of IL-1β. In addition, blockage of pyroptosis by caspase-1 inhibitor not only recovered the severe cornea pathology developed in Trem2 -/- mice but also restored the P. aeruginosa clearance suppressed by TREM2 deficiency. Our study demonstrated that TREM2 promotes host resistance against P. aeruginosa keratitis by inhibiting caspase-1-dependent pyroptosis, which provides new insights of TREM2-mediated anti-bacterial immunity.