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

Abstract

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 <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) keratitis. We found that <i>P. aeruginosa</i> keratitis was more severe in <i>Trem2</i>^-/- 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 <i>Trem2</i>^-/- mice but also restored the <i>P. aeruginosa</i> clearance suppressed by TREM2 deficiency. Our study demonstrated that TREM2 promotes host resistance against <i>P. aeruginosa</i> keratitis by inhibiting caspase-1-dependent pyroptosis, which provides new insights of TREM2-mediated anti-bacterial immunity.