{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mehto S"],"funding":["European Molecular Biology Organization","Department of Science and Technology, Ministry of Science and Technology, India","DBT/Wellcome Trust India Alliance","Wellcome Trust","Department of Biotechnology, Ministry of Science and Technology, India"],"pagination":["e111289"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9713718"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(23)"],"pubmed_abstract":["The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-κB 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-κB 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-κB 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."],"journal":["The EMBO journal"],"pubmed_title":["Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection."],"pmcid":["PMC9713718"],"funding_grant_id":["DST/INSPIRE/04/2019/001857","BT/PR45223/MED/29/1613/2022","IA/I/15/2/502071"],"pubmed_authors":["Chauhan S","Samal P","Sahu R","Kufer TA","Prasad P","Patnaik S","Dhar K","Bal R","Jaiswal P","Rusten TE","Sahoo BS","Jena KK","Jain A","Krishna S","Mehto S","Priyadarsini S","Murmu KC","Chauhan NR","Yadav R"],"additional_accession":[]},"is_claimable":false,"name":"Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.","description":"The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-κB 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-κB 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-κB 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-06-21T03:20:55.931Z","creation":"2025-02-19T03:56:07.337Z"},"accession":"S-EPMC9713718","cross_references":{"pubmed":["36221902"],"doi":["10.15252/embj.2022111289"]}}