RIPosomes are targets of IRGM-SQSTM1-dependent autophagy.
Subhash MehtoSoumya KunduSwati ChauhanSantosh ChauhanPublished in: Autophagy (2023)
The NOD1-NOD2-RIPK2-NFKB/NF-κB pro-inflammatory axis plays a significant role in regulating the immune response to bacterial infection. However, an excess of NFKB-dependent cytokine response can be detrimental and, thus, should be kept under control to maintain the innate immune balance. In our recent study, first, we showed that bacterial infection induces the biogenesis of RIPK2 oligomers (RIPosomes) that are recruited around the bacteria to enhance an NFKB-dependent pro-inflammatory response. Next, we showed that SQSTM1- and IRGM-dependent selective macroautophagy/autophagy degrades RIPosomes and their components to limit NOD1-NOD2-RIPK2-NFKB pro-inflammatory signaling. Consistently, depletion of IRGM results in an augmented RIPK2-dependent pro-inflammatory cytokine response induced by Shigella flexneri and Salmonella typhimurium . Further, bacterial infection- and DSS-induced gut inflammation in irgm1 KO mice is dampened upon therapeutic inhibition of RIPK2. Taken together, we showed that autophagy selectively degrades RIPosomes to suppress inflammation and maintain innate immune homeostasis.
Keyphrases
- innate immune
- oxidative stress
- signaling pathway
- inflammatory response
- cell death
- endoplasmic reticulum stress
- diabetic rats
- escherichia coli
- adipose tissue
- metabolic syndrome
- type diabetes
- lipopolysaccharide induced
- cell proliferation
- pi k akt
- insulin resistance
- listeria monocytogenes
- anti inflammatory
- stress induced