Molecular mechanisms of inflammasome activation during microbial infections

P Broz, DM Monack - Immunological reviews, 2011 - Wiley Online Library
P Broz, DM Monack
Immunological reviews, 2011Wiley Online Library
The innate immune system plays a crucial role in the rapid recognition and elimination of
invading microbes. Detection of microbes relies on germ‐line encoded pattern recognition
receptors (PRRs) that recognize essential bacterial molecules, so‐called pathogen‐
associated molecular patterns (PAMPs). A subset of PRRs, belonging to the NOD‐like
receptor (NLR) and the PYHIN protein families, detects viral and bacterial pathogens in the
cytosol of host cells and induces the assembly of a multi‐protein signaling platform called …
Summary
The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ‐line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so‐called pathogen‐associated molecular patterns (PAMPs). A subset of PRRs, belonging to the NOD‐like receptor (NLR) and the PYHIN protein families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi‐protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the mammalian cysteine protease caspase‐1, a central mediator of innate immunity. Active caspase‐1 promotes the maturation and release of interleukin‐1β (IL‐1β) and IL‐18 as well as protein involved in cytoprotection and tissue repair. In addition, caspase‐1 initiates a novel form of cell death called pyroptosis. Here, we discuss latest advances and our insights on inflammasome stimulation by two model intracellular pathogens, Francisella tularensis and Salmonella typhimurium. Recent studies on these pathogens have significantly shaped our understanding of the molecular mechanisms of inflammasome activation and how microbes can evade or manipulate inflammasome activity. In addition, we review the role of the inflammasome adapter ASC in caspase‐1 autoproteolysis and new insights into the structure of the inflammasome complex.
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