Caspase-1-induced Pyroptosis is an Innate Immune Effector Mechanism Against Intracellular Bacteria

Overview

Journal Nat Immunol

Date 2010 Nov 9

PMID 21057511

Citations 715

Authors

Edward A Miao

Irina A Leaf

Piper M Treuting

Dat P Mao

Monica Dors

Anasuya Sarkar

Sarah E Warren

Mark D Wewers

Alan Aderem

Affiliations

Soon will be listed here.

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.

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