An important role of prostanoid receptor EP2 in host resistance to mycobacterium tuberculosis infection in mice

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis, resides and replicates within susceptible hosts by inhibiting host antimicrobial mechanisms. Prostaglandin E₂ (PGE₂), produced by M. tuberculosis–infected macrophages, exerts a variety of immunomodulatory functions via 4 receptors (EP1–EP4), each mediating distinct PGE₂ functions. Here, we show that M. tuberculosis infection selectively upregulates EP2 messenger RNA expression in CD4⁺ T cells. We found that EP2 deficiency in mice increases susceptibility to M. tuberculosis infection, which correlated with reduced antigen-specific T-cell responses and increased levels of CD4⁺CD25⁺Foxp3⁺ T-regulatory cells. These findings have revealed an important role for EP2 in host immune defense against tuberculosis. As a G protein-coupled receptor, EP2 could serve as a target for immunotherapy of tuberculosis.