Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.

The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-?B pro-inflammatory response against invading pathogens. However, uncontrolled NF-?B signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-?B innate immune axis is activated and resolved remain poorly understood. Here, we demonstrate that bacterial infection ...
induces the formation of endogenous RIPK2 oligomers (RIPosomes) that are self-assembling entities that coat the bacteria to induce NF-?B response. Next, we show that autophagy proteins IRGM and p62/SQSTM1 physically interact with NOD1/2, RIPK2 and RIPosomes to promote their selective autophagy and limit NF-?B activation. IRGM suppresses RIPK2-dependent pro-inflammatory programs induced by Shigella and Salmonella. Consistently, the therapeutic inhibition of RIPK2 ameliorates Shigella infection- and DSS-induced gut inflammation in Irgm1 KO mice. This study identifies a unique mechanism where the innate immune proteins and autophagy machinery are recruited together to the bacteria for defense as well as for maintaining immune homeostasis.
Mesh Terms:
Animals, Autophagy, Bacterial Infections, Homeostasis, Immunity, Innate, Mice, Mice, Inbred NOD, NF-kappa B
EMBO J
Date: Dec. 01, 2022
Download Curated Data For This Publication
246351
Switch View:
  • Interactions 17