Publication Date:
2013-01-26
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697099/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aachoui, Youssef -- Leaf, Irina A -- Hagar, Jon A -- Fontana, Mary F -- Campos, Cristine G -- Zak, Daniel E -- Tan, Michael H -- Cotter, Peggy A -- Vance, Russell E -- Aderem, Alan -- Miao, Edward A -- 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/ -- New York, N.Y. -- Science. 2013 Feb 22;339(6122):975-8. doi: 10.1126/science.1230751. Epub 2013 Jan 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23348507" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
