Bacterial Outer Membrane Vesicle-Mediated Cytosolic Delivery of Flagellin Triggers Host NLRC4 Canonical Inflammasome Signaling
Autor: | Joon Haeng Rhee, Je-Wook Yu, Eun Ju Lee, Eunjin Lee, Jungmin Yang, Sung Jae Shin, Inhwa Hwang |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Salmonella typhimurium
0301 basic medicine Inflammasomes Interleukin-1beta caspase-1 flagellin Mice Cytosol 0302 clinical medicine NLRC4 Immunology and Allergy Original Research Mice Knockout biology Chemistry Caspase 1 Inflammasome Endocytosis Cell biology host defense Bacterial outer membrane outer membrane vesicles Signal Transduction medicine.drug lcsh:Immunologic diseases. Allergy Bacterial outer membrane vesicles Immunology 03 medical and health sciences Bacterial Proteins GTP-Binding Proteins inflammasome NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Secretion Innate immune system Host Microbial Interactions Macrophages Calcium-Binding Proteins Models Immunological Immunity Innate Enzyme Activation Mice Inbred C57BL Bacterial Outer Membrane 030104 developmental biology biology.protein Apoptosis Regulatory Proteins lcsh:RC581-607 Flagellin interleukin-1 030215 immunology |
Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
ISSN: | 1664-3224 |
Popis: | Bacteria-released components can modulate host innate immune response in the absence of direct host cell–bacteria interaction. In particular, bacteria-derived outer membrane vesicles (OMVs) were recently shown to activate host caspase-11-mediated non-canonical inflammasome pathway via deliverance of OMV-bound lipopolysaccharide. However, further precise understanding of innate immune-modulation by bacterial OMVs remains elusive. Here, we present evidence that flagellated bacteria-released OMVs can trigger NLRC4 canonical inflammasome activation via flagellin delivery to the cytoplasm of host cells. Salmonella typhimurium-derived OMVs caused a robust NLRC4-mediated caspase-1 activation and interleukin-1β secretion in macrophages in an endocytosis-dependent, but guanylate-binding protein-independent manner. Notably, OMV-associated flagellin is crucial for Salmonella OMV-induced inflammasome response. Flagellated Pseudomonas aeruginosa-released OMVs consistently promoted robust NLRC4 inflammasome activation, while non-flagellated Escherichia coli-released OMVs induced NLRC4-independent non-canonical inflammasome activation leading to NLRP3-mediated interleukin-1β secretion. Flagellin-deficient Salmonella OMVs caused a weak interleukin-1β production in a NLRP3-dependent manner. These findings indicate that Salmonella OMV triggers NLRC4 inflammasome activation via OMV-associated flagellin in addition to a mild induction of non-canonical inflammasome signaling via OMV-bound lipopolysaccharide. Intriguingly, flagellated Salmonella-derived OMVs induced more rapid inflammasome response than flagellin-deficient Salmonella OMV and non-flagellated Escherichia coli-derived OMVs. Supporting these in vitro results, Nlrc4-deficient mice showed significantly reduced interleukin-1β production after intraperitoneal challenge with Salmonella-released OMVs. Taken together, our results here propose that NLRC4 inflammasome machinery is a rapid sensor of bacterial OMV-bound flagellin as a host defense mechanism against bacterial pathogen infection. |
Databáze: | OpenAIRE |
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