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Innate immune sensing of a bacterial protein in the ER by IRE1α
Author(s) -
Cho Jin Ah,
Lencer Wayne
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.866.2
Subject(s) - endoplasmic reticulum , innate immune system , unfolded protein response , xbp1 , microbiology and biotechnology , effector , biology , endoplasmic reticulum associated protein degradation , immune system , rna splicing , rna , gene , immunology , biochemistry
The plasma membrane and all membrane‐bound organelles except for the Golgi and endoplasmic reticulum (ER) are equipped with pattern‐recognition molecules to sense microbes or their products and induce innate immunity for host defense. Here, we report that Inositol‐REquiring‐1α (IRE1α), an ER protein that signals in the unfolded protein response (UPR), is activated to induce inflammation by cholera and Shiga toxins as they co‐opt the ER to cause disease. Other known UPR transducers, including the IRE1α effector XBP1 are dispensable for this signaling. The inflammatory response depends instead on the RNase activity of IRE1α and retinoic‐acid inducible gene 1 (RIG‐I), a cytosolic sensor of RNA fragments. These observations implicate Regulated IRE1α‐Dependent Decay of mRNA (RIDD) in a novel innate immune mechanism of host defense originating from within the ER lumen. Grant Funding Source : NIH R01/CCFA