1. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
- Author
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Anasuya Sarkar, Piper M. Treuting, Dat P. Mao, Sarah E. Warren, Mark D. Wewers, Irina A. Leaf, Monica Dors, Edward A. Miao, and Alan Aderem
- Subjects
Salmonella typhimurium ,Inflammasomes ,Immunology ,Caspase 1 ,Apoptosis ,Enzyme-Linked Immunosorbent Assay ,Cell Separation ,Caspase-11 ,Biology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Immunology and Allergy ,Secretion ,030304 developmental biology ,0303 health sciences ,Innate immune system ,pyroptosis ,Macrophages ,Intracellular parasite ,Calcium-Binding Proteins ,Pyroptosis ,Inflammasome ,Flow Cytometry ,Immunohistochemistry ,Immunity, Innate ,Cell biology ,Mice, Inbred C57BL ,IL-1β Salmonella ,cell death ,Caspase-1 ,Salmonella Infections ,biology.protein ,bacteria ,Apoptosis Regulatory Proteins ,Flagellin ,030215 immunology ,medicine.drug - Abstract
Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1β (IL-1β) 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-1β 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-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.
- Published
- 2010