Document Detail


Caspase-11 protects against bacteria that escape the vacuole.
MedLine Citation:
PMID:  23348507     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caspases are either apoptotic or inflammatory. Among inflammatory caspases, caspase-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in inflammatory disease, only caspase-1 has an established protective role during infection. Here, we report that caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. Although Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) aberrantly enter the cytosol. These mutants triggered caspase-11, which enhanced clearance of S. typhimurium sifA in vivo. This response did not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also triggered caspase-11, which protected mice from lethal challenge with B. thailandensis and B. pseudomallei. Thus, caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens.
Authors:
Youssef Aachoui; Irina A Leaf; Jon A Hagar; Mary F Fontana; Cristine G Campos; Daniel E Zak; Michael H Tan; Peggy A Cotter; Russell E Vance; Alan Aderem; Edward A Miao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-24
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  339     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-03-05     Revised Date:  2014-09-26    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  975-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Burkholderia / pathogenicity,  physiology
Burkholderia Infections / enzymology,  immunology,  metabolism
Burkholderia pseudomallei / pathogenicity,  physiology
Caspases / metabolism*
Cell Death*
Cytosol / microbiology*
Gram-Negative Bacterial Infections / enzymology,  immunology*,  microbiology
Immunity, Innate
Inflammasomes / metabolism
Macrophages / immunology,  microbiology*
Mice
Mice, Inbred C57BL
Phagosomes / microbiology
Salmonella Infections, Animal / enzymology,  immunology,  microbiology
Salmonella typhimurium / pathogenicity,  physiology
Vacuoles / microbiology*
Grant Support
ID/Acronym/Agency:
AI057141/AI/NIAID NIH HHS; AI063302/AI/NIAID NIH HHS; AI065359/AI/NIAID NIH HHS; AI075039/AI/NIAID NIH HHS; AI080749/AI/NIAID NIH HHS; AI097518/AI/NIAID NIH HHS; P01 AI063302/AI/NIAID NIH HHS; P30 CA016086/CA/NCI NIH HHS; R01 AI075039/AI/NIAID NIH HHS; R01 AI080749/AI/NIAID NIH HHS; R01 AI097518/AI/NIAID NIH HHS; U19 AI100627/AI/NIAID NIH HHS; U54 AI057141/AI/NIAID NIH HHS; U54 AI065359/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Inflammasomes; EC 3.4.22.-/Casp11 protein, mouse; EC 3.4.22.-/Caspases
Comments/Corrections
Comment In:
Cell Host Microbe. 2013 Mar 13;13(3):243-5   [PMID:  23498948 ]
Science. 2013 Feb 22;339(6122):912-3   [PMID:  23430642 ]
Nat Rev Immunol. 2013 Mar;13(3):154-5   [PMID:  23411795 ]

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