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Interferon-induced guanylate-binding proteins promote cytosolic lipopolysaccharide detection by caspase-11.
DNA and Cell Biology
Lipopolysaccharide (LPS) from gram-negative bacteria is a classical pathogen-associated molecular pattern and a strong inducer of immune responses. While the detection of LPS on the cell surface and in the endosome by Toll-like receptor 4 (TLR4) has been studied for some time, it has only recently been discovered that LPS can also be sensed in the cytosol of cells by a noncanonical inflammasome pathway, resulting in the activation of the cysteine protease caspase-11. Intriguingly, activation of this pathway requires the production of interferons (IFNs) and the induction of a class of IFN-induced GTPases called guanylate-binding proteins (GBPs), which have previously been linked to cell-autonomous killing of intracellular microbes. In this study, we review the recent advances in our understanding of cytosolic LPS sensing and the function of mammalian GBPs.
Animals, Caspases/physiology, Cytoplasm/enzymology, Cytoplasm/immunology, GTP-Binding Proteins/physiology, Humans, Immunity, Innate, Inflammasomes/physiology, Interferons/physiology, Lipopolysaccharides/pharmacology
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