Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation

SUMMARY

Blood neutrophils perform an essential host-defense function by directly migrating to bacterial invasion sites to kill bacteria. The mechanisms mediating the transition from the migratory to bactericidal phenotype remain elusive. Here, we demonstrate that TRPM2, a trp superfamily member, senses neutrophil-generated reactive oxygen species and restrains neutrophil migration. The inhibitory function of oxidant sensing by TRPM2 requires the oxidation of Cys549, which then induces TRMP2 binding to formyl peptide receptor 1 (FPR1) and subsequent FPR1 internalization and signaling inhibition. The oxidant sensing-induced termination of neutrophil migration at the site of infection permits a smooth transition to the subsequent microbial killing phase.

In Brief

The molecular switches that turn a chemotactic neutrophil into a microbial killing machine are still unclear. Wang et al. show that, upon reaching the site of infection, increased ROS production by neutrophils—via a respiratory burst sensed by neutrophil TRPM2—stops cell migration and promotes a switch to microbial killing.