Caspase-11 Protects Against Bacteria That Escape the Vacuole

TLDR

Caspases are either apoptotic or inflammatory, and among the inflammatory ones, caspase‑1 and caspase‑11 trigger pyroptosis; while caspase‑1 has a known protective role during infection, caspase‑11’s role has been unclear. The study investigates whether caspase‑11 is required for innate immunity against cytosolic bacteria. Caspase‑11 is essential for clearing cytosolic bacteria such as Salmonella sifA, Legionella sdhA, and Burkholderia species, acting independently of inflammasome pathways and protecting mice from lethal infection.

Abstract

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.