Pathogen effector-triggered aggregation of TIR-1/SARM1 on lysosome-related organelles activates intestinal immunity

Abstract

SUMMARYMechanisms of pathogen recognition in barrier tissues, which interface with both commensal and virulent bacteria, are critical for health and not fully understood. Here, we discovered a central role for lysosome-related organelles in innate immune sensing and p38 innate immune activation in intestinal epithelial cells, which enables the nematodeC. elegansto survey for the effects of a bacterial pathogen on the host to activate protective anti-pathogen defenses. We showed that the conserved immune signaling regulator TIR-1/SARM1 is expressed on the membranes of lysosome-related organelles. Pyocyanin, a virulence effector secreted byPseudomonas aeruginosa,alkalinized and collapsed lysosome-related organelles, triggering TIR-1/SARM1 multimerization to activate the p38 innate immune pathway. Thus, pathogen effector-mediated collapse of lysosome-related organelles is an initiating event of innate immune sensing and p38 activation, which allowsC. elegansto identify a pathogen through its effects on host physiology.