Caspase-11 Protects Against Bacteria That Escape the Vacuole
Caspase-11 Protects Against Bacteria That Escape the Vacuole
Youssef Aachoui, et al. 2013. Science. 339:975-8.
Speaker: Shu-Ting Lu (呂淑婷) Time: 15:10~16:00, Apr. 3, 2013
Commentator: Dr. Chih-Peng Chang (張志鵬 老師) Place: Room 601
Abstract:
Canonical inflammasomes, such as NLRP3, AIM2, and NLRC4, detect intracellular PAMPs and activate caspase-1, ultimately cause secretion of proinflammatory cytokines (1). Activation of inflammasomes can also lead to an inflammatory cell death program, named pyroptosis. Although a role for caspase-1 downstream of inflammasomes is well characterized, the discovery that caspase-1 knockout mice were also deficient in caspase-11 has led to a reassessment of the function of caspase-11. Gram negative bacteria, Burkholderia thailandensis and B. pseudomallei, that use type III secretion system (T3SS) to invade the cytosol, induce NLRP3 and NLRC4 inflammasome activation and promote IL-1b production. However, the murine survival rate and the cytotoxicity only impaired in Casp1-/-Casp11-/- , rather than Nlrc4-/-ASC-/- and IL1b-/-/18-/- mice. The authors found thatB. thailandensis T3SS which facilitates bacteria entering the cytosol is required for induction of pyroptosis, so they further use Salmonella typhimurium and Legionella pneumophila specific mutants (sifA and sdhA, respectively) to investigate the inflammasome activation effect on vacuole escaped bacteria. In concert with B. pseudomallei, diverse cytosolic bacteria activate pyroptosis independent of NLRC4, NLRP3 and ASC. After complement Casp1-/-Casp11-/- macrophages with Casp1 or Casp11, they found that caspase-11 alone promote pyroptosis without IL-1β secretion. Through co-infection of will-type and ∆sifA S. typhimurium, the authors showed that both caspas-1- and caspase-11- dependent pyroptosis are likely to be the mechanism of bacterial clearance in vivo. It is the first time that caspase-11 be reported to protect animals from lethal infection by vacuole escaped bacteria through caspase-1 independent pyroptosis (2).
References:
1. E. A. Miao., et al. 2011. Caspase-1-induced pyroptotic cell death. Immunol. Rev. 243, 206.
2. Marija Cemma and John H. Brumell. 2013. Bacterial Escape Artists Set Afire. Science 339, 912.