| First Author | Mehto S | Year | 2022 |
| Journal | EMBO J | Volume | 41 |
| Issue | 23 | Pages | e111289 |
| PubMed ID | 36221902 | Mgi Jnum | J:332005 |
| Mgi Id | MGI:7408014 | Doi | 10.15252/embj.2022111289 |
| Citation | Mehto S, et al. (2022) Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection. EMBO J 41(23):e111289 |
| abstractText | The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-kappaB pro-inflammatory response against invading pathogens. However, uncontrolled NF-kappaB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-kappaB 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-kappaB 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-kappaB 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. |
