Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria
Autor: | Santos, José Carlos, Boucher, Dave, Schneider, Larisa Kapinos, Demarco, Benjamin, Dilucca, Marisa, Shkarina, Kateryna, Heilig, Rosalie, Chen, Kaiwen W., Lim, Roderick Y. H., Broz, Petr |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Lipopolysaccharides
Pattern recognition receptors Inflammasomes Science Static Electricity Article Cell Line Inflammasome Cytosol GTP-Binding Proteins Salmonella Pyroptosis Humans lcsh:Science Innate immunity Intracellular Signaling Peptides and Proteins Epithelial Cells Phosphate-Binding Proteins Caspases Initiator Enzyme Activation lcsh:Q lipids (amino acids peptides and proteins) Infection HeLa Cells Protein Binding |
Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature communications, vol. 11, no. 1, pp. 3276 |
ISSN: | 2041-1723 |
Popis: | The human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic Salmonella or upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolic Salmonella seconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling. Detection of LPS derived from Gram-negative bacteria by innate immune receptors is a critical step in the host response. Here Santos and colleagues show human GBP1 binds to LPS resulting in non-canonical inflammasome activation. |
Databáze: | OpenAIRE |
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