| First Author | Miao EA | Year | 2010 |
| Journal | Nat Immunol | Volume | 11 |
| Issue | 12 | Pages | 1136-42 |
| PubMed ID | 21057511 | Mgi Jnum | J:167323 |
| Mgi Id | MGI:4867799 | Doi | 10.1038/ni.1960 |
| Citation | Miao EA, et al. (2010) Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol 11(12):1136-42 |
| abstractText | Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1beta (IL-1beta) and IL-18. Although infection with wild-type Salmonella typhimurium is lethal to mice, we show here that a strain that persistently expresses flagellin was cleared by the cytosolic flagellin-detection pathway through the activation of caspase-1 by the NLRC4 inflammasome; however, this clearance was independent of IL-1beta and IL-18. Instead, caspase-1-induced pyroptotic cell death released bacteria from macrophages and exposed the bacteria to uptake and killing by reactive oxygen species in neutrophils. Similarly, activation of caspase-1 cleared unmanipulated Legionella pneumophila and Burkholderia thailandensis by cytokine-independent mechanisms. This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1beta and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system. |
