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Recognition of Intracellular Bacteria by Inflammasomes

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  • Author: Petr Broz1
  • Editors: Pascale Cossart2, Craig R. Roy3, Philippe Sansonetti4
    Affiliations: 1: Department of Biochemistry, University of Lausanne, Switzerland; 2: Institut Pasteur, Paris, France; 3: Yale University School of Medicine, New Haven, Connecticut; 4: Institut Pasteur, Paris, France
  • Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0003-2019
  • Received 26 March 2018 Accepted 17 May 2018 Published 08 March 2019
  • Petr Broz, [email protected]
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  • Abstract:

    Inflammasomes are multiprotein signaling complexes that are assembled by cytosolic sensors upon the detection of infectious or noxious stimuli. These complexes activate inflammatory caspases to induce host cell death and cytokine secretion and are an essential part of antimicrobial host defense. In this review, I discuss how intracellular bacteria are detected by inflammasomes, how the specific sensing mechanism of each inflammasome receptor restricts the ability of bacteria to evade immune recognition, and how host cell death is used to control bacterial replication .

  • Citation: Broz P. 2019. Recognition of Intracellular Bacteria by Inflammasomes. Microbiol Spectrum 7(2):BAI-0003-2019. doi:10.1128/microbiolspec.BAI-0003-2019.


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Inflammasomes are multiprotein signaling complexes that are assembled by cytosolic sensors upon the detection of infectious or noxious stimuli. These complexes activate inflammatory caspases to induce host cell death and cytokine secretion and are an essential part of antimicrobial host defense. In this review, I discuss how intracellular bacteria are detected by inflammasomes, how the specific sensing mechanism of each inflammasome receptor restricts the ability of bacteria to evade immune recognition, and how host cell death is used to control bacterial replication .

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Image of FIGURE 1

Activation of canonical and noncanonical inflammasomes by bacteria. () Inflammasome receptors use different recognition mechanisms to sense bacterial infections. The NAIP-NLRC4 and AIM2 pathways involve direct binding of the respective ligands (flagellin, T3SS structural proteins, or DNA). Nlrp1b recognizes the proteolytic activity of the metalloprotease lethal factor from by serving as a decoy substrate. Pyrin uses a guard mechanism to detect the inactivation of RhoA. The kinase activities of RhoA and PNK1/2 are required to keep pyrin in an inactive state, in which it is phosphorylated and bound by 14-3-3 proteins. NLRP3 activation involves priming by signal 1, followed by activation by signal 2. The nature of signal 2 and the mechanism of recognition are yet unknown, but they are linked to membrane permeabilization, K efflux, and mitochondrial dysfunction. The noncanonical pathway involves direct detection of LPS by caspase-11 in mice or caspase-4 (or caspase-5) in humans. () Following activation, inflammasome receptors oligomerize and recruit the bipartite adaptor ASC, which forms long filaments that cluster to form the ASC speck. Pro-caspase-1 is recruited to the filaments by CARD-CARD interaction and activated by dimerization and autoproteolysis. () Active caspase-1 and caspase-11 process GSDMD, removing the regulatory C-terminal domain and unleashing the cytotoxic activity of the N-terminal fragment. The GSDMD N terminus is inserted into the plasma membrane and forms large pores, which disrupt the electrochemical gradient and induce pyroptosis. Caspase-1 also processes IL-1 family cytokines (like IL-1b) and promotes their release from cells in a pathway that is at least partially GSDMD dependent.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0003-2019
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Image of FIGURE 2

Antimicrobial effects of pyroptosis. () Activation of canonical or noncanonical inflammasomes in infected phagocytes results in the formation of GSDMD pores and pyroptosis. Intracellular bacteria are trapped within pyroptotic cell bodies, called PITs. GSDMD pores can potentially also damage intracellular bacteria. PITs are recognized and efferocytosed by neutrophils, which efficiently kill PIT-associated bacteria. () Engagement of pyroptosis in IECs promotes the expulsion of pyroptotic cells from the epithelial cell layer into the gut lumen. Any associated bacteria are removed with the dying cells and expelled from the intestines.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0003-2019
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