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PMID: 18070936 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome.

The Journal of experimental medicine ·Vol. 204 ·No. 13 ·2007-12-24 ·Pages 3235-45

Sutterwala FS, Mijares LA, Li L, Ogura Y, Kazmierczak BI, Flavell RA

Abstract

Pseudomonas aeruginosa is a Gram-negative bacterium that causes opportunistic infections in immunocompromised individuals. P. aeruginosa employs a type III secretion system to inject effector molecules into the cytoplasm of the host cell. This interaction with the host cell leads to inflammatory responses that eventually result in cell death. We show that infection of macrophages with P. aeruginosa results in activation of caspase-1 in an IPAF-dependent, but flagellin-independent, manner. Macrophages deficient in IPAF or caspase-1 were markedly resistant to P. aeruginosa-induced cell death and release of the proinflammatory cytokine interleukin (IL)-1beta. A subset of P. aeruginosa isolates express the effector molecule exoenzyme U (ExoU), which we demonstrate is capable of inhibiting caspase-1-driven proinflammatory cytokine production. This study shows a key role for IPAF and capase-1 in innate immune responses to the pathogen P. aeruginosa, and also demonstrates that virulent ExoU-expressing strains of P. aeruginosa can circumvent this innate immune response.

MeSH Terms
Animals Apoptosis Regulatory Proteins/metabolism Calcium-Binding Proteins/metabolism Caspase 1/metabolism Cell Death Cytoplasm/metabolism Enzyme Activation Flagellin/metabolism Inflammation Interleukin-1beta/metabolism Kinetics Macrophages/metabolism Mice Mice, Inbred C57BL Models, Biological Pseudomonas Infections/immunology Pseudomonas aeruginosa/metabolism
Chemicals
Apoptosis Regulatory Proteins Calcium-Binding Proteins Interleukin-1beta Ipaf protein, mouse Flagellin Caspase 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sutterwala Fayyaz S
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Mijares Lilia A
Li Li
Ogura Yasunori
Kazmierczak Barbara I
Flavell Richard A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20071239
Published
2007-12-24
Epub
2007-00-10
Pages
3235-45
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2150987
Subset
IM
Grants
NIAID NIH HHS · F31 AI061882 · United States
NIAID NIH HHS · K08 AI065517 · United States
NIAID NIH HHS · R01 AI054920 · United States
External Links
PubMed source DOI: 10.1084/jem.20071239 PMC Full Text View journal details
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