Caspase-11 protects against bacteria that escape the vacuole.
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.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Youssef
Y
Aachoui
Irina A
IA
Leaf
Jon A
JA
Hagar
Mary F
MF
Fontana
Cristine G
CG
Campos
Daniel E
DE
Zak
Michael H
MH
Tan
Peggy A
PA
Cotter
Russell E
RE
Vance
Alan
A
Aderem
Edward A
EA
Miao
D000818:Animals; D019117:Burkholderia / Q000472:pathogenicity / Q000502:physiology; D019121:Burkholderia Infections / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D016957:Burkholderia pseudomallei / Q000472:pathogenicity / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D053471:Caspases, Initiator; D016923:Cell Death; D003600:Cytosol / Q000382:microbiology*; D016905:Gram-Negative Bacterial Infections / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000382:microbiology; D012481:Salmonella Infections, Animal / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology; D014617:Vacuoles / Q000382:microbiology*
D058847:Inflammasomes; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator