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-1 beta (IL-1 beta) 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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Univ Washington, Dept Microbiol, Seattle, WA 98195 USAUniv Washington, Dept Microbiol, Seattle, WA 98195 USA
Bergsbaken, Tessa
Fink, Susan L.
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Univ Washington, Dept Mol & Cellular Biol, Seattle, WA 98195 USAUniv Washington, Dept Microbiol, Seattle, WA 98195 USA
Fink, Susan L.
Cookson, Brad T.
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Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
Univ Washington, Dept Lab Med, Seattle, WA 98195 USAUniv Washington, Dept Microbiol, Seattle, WA 98195 USA
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Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Brodsky, Igor E.
Palm, Noah W.
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Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Palm, Noah W.
Sadanand, Saheli
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Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Sadanand, Saheli
Ryndak, Michelle B.
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SUNY Stony Brook, Sch Med, Ctr Infect Dis, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Ryndak, Michelle B.
Sutterwala, Fayyaz S.
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Univ Iowa, Div Infect Dis, Iowa City, IA 52242 USA
Univ Iowa, Dept Internal Med, Inflammat Program, Iowa City, IA 52242 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Sutterwala, Fayyaz S.
Flavell, Richard A.
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Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Flavell, Richard A.
Bliska, James B.
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SUNY Stony Brook, Sch Med, Ctr Infect Dis, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Bliska, James B.
Medzhitov, Ruslan
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机构:
Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
机构:
Univ Washington, Dept Microbiol, Seattle, WA 98195 USAUniv Washington, Dept Microbiol, Seattle, WA 98195 USA
Bergsbaken, Tessa
Fink, Susan L.
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h-index: 0
机构:
Univ Washington, Dept Mol & Cellular Biol, Seattle, WA 98195 USAUniv Washington, Dept Microbiol, Seattle, WA 98195 USA
Fink, Susan L.
Cookson, Brad T.
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h-index: 0
机构:
Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
Univ Washington, Dept Lab Med, Seattle, WA 98195 USAUniv Washington, Dept Microbiol, Seattle, WA 98195 USA
机构:
Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Brodsky, Igor E.
Palm, Noah W.
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h-index: 0
机构:
Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Palm, Noah W.
Sadanand, Saheli
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h-index: 0
机构:
Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Sadanand, Saheli
Ryndak, Michelle B.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Sch Med, Ctr Infect Dis, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Ryndak, Michelle B.
Sutterwala, Fayyaz S.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Iowa, Div Infect Dis, Iowa City, IA 52242 USA
Univ Iowa, Dept Internal Med, Inflammat Program, Iowa City, IA 52242 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Sutterwala, Fayyaz S.
Flavell, Richard A.
论文数: 0引用数: 0
h-index: 0
机构:
Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Flavell, Richard A.
Bliska, James B.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Sch Med, Ctr Infect Dis, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Bliska, James B.
Medzhitov, Ruslan
论文数: 0引用数: 0
h-index: 0
机构:
Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USAYale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA