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
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
Externí odkaz: