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PMID: 18724372 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin.

Nature immunology ·Vol. 9 ·No. 10 ·2008-10-00 ·Pages 1171-8

Lightfield KL, Persson J, Brubaker SW, Witte CE, von Moltke J, Dunipace EA, Henry T, Sun YH, Cado D, Dietrich WF, Monack DM, Tsolis RM, Vance RE

Abstract

Inflammasomes are cytosolic multiprotein complexes that sense microbial infection and trigger cytokine production and cell death. However, the molecular components of inflammasomes and what they sense remain poorly defined. Here we demonstrate that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome activation in the absence of bacterial contaminants or secretion systems. To further elucidate the host flagellin-sensing pathway, we generated mice deficient in the intracellular sensor Naip5. These mice failed to activate the inflammasome in response to the 35 amino acids of flagellin or in response to Legionella pneumophila infection. Our data clarify the molecular basis for the cytosolic response to flagellin.

MeSH Terms
Amino Acid Motifs/immunology Animals Apoptosis Regulatory Proteins/immunology,metabolism Calcium-Binding Proteins/immunology,metabolism Cytosol Enzyme-Linked Immunosorbent Assay Flagellin/chemistry,immunology Immunoblotting Legionella pneumophila/immunology Legionnaires' Disease/immunology Macrophages/immunology,microbiology Mice Multiprotein Complexes/immunology Neuronal Apoptosis-Inhibitory Protein/genetics,immunology Toll-Like Receptor 5/immunology,metabolism Transduction, Genetic
Chemicals
Apoptosis Regulatory Proteins Calcium-Binding Proteins Ipaf protein, mouse Multiprotein Complexes Naip5 protein, mouse Neuronal Apoptosis-Inhibitory Protein Toll-Like Receptor 5 Flagellin
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Lightfield Karla L
School of Public Health, University of California, Berkeley, CA 94720, USA.
Persson Jenny
Brubaker Sky W
Witte Chelsea E
von Moltke Jakob
Dunipace Eric A
Henry Thomas
Sun Yao-Hui
Cado Dragana
Dietrich William F
Monack Denise M
Tsolis Renée M
Vance Russell E
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1646
Published
2008-10-00
Epub
2008-00-24
Pages
1171-8
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2614210
Subset
IM
Grants
NIAID NIH HHS · K22 AI070739 · United States
NIAID NIH HHS · R01 AI075039 · United States
NIAID NIH HHS · K22 AI070739-02 · United States
NIAID NIH HHS · AI075039 · United States
NIAID NIH HHS · R01 AI075039-01A2 · United States
NIAID NIH HHS · AI070739 · United States
External Links
PubMed source DOI: 10.1038/ni.1646 PMC Full Text View journal details
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