Necroptosis mediators RIPK3 and MLKL suppress intracellular Listeria replication independently of host cell killing

RIPK3, a key mediator of necroptosis, has been implicated in the host defense against viral infection primary in immune cells. However, gene expression analysis revealed that RIPK3 is abundantly expressed not only in immune organs but also in the gastrointestinal tract, particularly in the small int...

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Veröffentlicht in:The Journal of cell biology 2019-06, Vol.218 (6), p.1994-2005
Hauptverfasser: Sai, Kazuhito, Parsons, Cameron, House, John S, Kathariou, Sophia, Ninomiya-Tsuji, Jun
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container_end_page 2005
container_issue 6
container_start_page 1994
container_title The Journal of cell biology
container_volume 218
creator Sai, Kazuhito
Parsons, Cameron
House, John S
Kathariou, Sophia
Ninomiya-Tsuji, Jun
description RIPK3, a key mediator of necroptosis, has been implicated in the host defense against viral infection primary in immune cells. However, gene expression analysis revealed that RIPK3 is abundantly expressed not only in immune organs but also in the gastrointestinal tract, particularly in the small intestine. We found that orally inoculated , a bacterial foodborne pathogen, efficiently spread and caused systemic infection in -deficient mice while almost no dissemination was observed in wild-type mice. infection activated the RIPK3-MLKL pathway in cultured cells, which resulted in suppression of intracellular replication of Surprisingly, infection-induced phosphorylation of MLKL did not result in host cell killing. We found that MLKL directly binds to and inhibits their replication in the cytosol. Our findings have revealed a novel functional role of the RIPK3-MLKL pathway in nonimmune cell-derived host defense against invasion, which is mediated through cell death-independent mechanisms.
doi_str_mv 10.1083/jcb.201810014
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subjects Animals
Cell death
Cytosol
Disseminated infection
Female
Foodborne pathogens
Gastrointestinal system
Gastrointestinal tract
Gene expression
Humans
Immune system
Infections
Intracellular
Listeria
Listeria - growth & development
Listeria - immunology
Listeria - metabolism
Listeria monocytogenes
Listeriosis - metabolism
Listeriosis - microbiology
Listeriosis - pathology
Listeriosis - prevention & control
Mice
Mice, Inbred C57BL
Mice, Knockout
Necroptosis
Organs
Phosphorylation
Protein Kinases - physiology
Receptor-Interacting Protein Serine-Threonine Kinases - genetics
Receptor-Interacting Protein Serine-Threonine Kinases - metabolism
Receptor-Interacting Protein Serine-Threonine Kinases - physiology
Replication
Small intestine
title Necroptosis mediators RIPK3 and MLKL suppress intracellular Listeria replication independently of host cell killing
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