Caspase-11 Protects Against Bacteria That Escape the Vacuole

• DOI: 10.1126/science.1230751
• Publication Date: 2013-01-25T02:38:41Z
• 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
• Keywords: Pyroptosis

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 disease, only 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 Legionella pneumophila normally reside the vacuole, specific mutants (sifA sdhA, respectively) aberrantly enter cytosol. These triggered caspase-11, which enhanced clearance S. sifA vivo. This response did require NLRP3, NLRC4, ASC inflammasome pathways. Burkholderia species naturally invade cytosol also protected mice from lethal challenge with B. thailandensis pseudomallei. Thus, critical surviving exposure ubiquitous environmental pathogens.