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Activation and Evasion of Inflammasomes by Yersinia

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Inflammasome Signaling and Bacterial Infections

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 397))

Abstract

The innate immune system plays an essential role in initiating the early response against microbial infection, as well as instructing and shaping subsequent responses. Microbial pathogens are enormously diverse in terms of the niches they occupy, their metabolic properties and requirements, and the cellular pathways that they target. Nevertheless, innate sensing of pathogens triggers a relatively stereotyped set of responses that involve transcriptional induction of key inflammatory mediators, as well as post-translational assembly and activation of a multiprotein inflammatory complex termed ‘the inflammasome.’ Along with classical Pattern Recognition Receptors, the inflammasome activation pathway has emerged as a key regulator of tissue homeostasis and immune defense. Components of the inflammasome generally exist within the cell in a soluble, monomeric state, and oligomerize in response to diverse enzymatic activities associated with infection or cellular stress. Inflammasome assembly triggers activation of the pro-enzyme caspase-1, resulting in the cleavage of caspase-1 targets. The most extensively studied targets are the cytokines of the IL-1 family, but the recent discovery of Gasdermin D as a novel target of caspase-1 and the related inflammatory caspase, caspase-11, has begun to mechanistically define the links between caspase-1 activation and cell death. Cell death is a hallmark of macrophage infection by many pathogens, including the gram-negative bacterial pathogens of the genus Yersinia. Intriguingly, the activities of the Yersinia-secreted effector proteins and the type III secretion system (T3SS) itself have been linked to both inflammasome activation and evasion during infection. The balance between these activating and inhibitory activities shapes the outcome of Yersinia infection. Here, we describe the current state of knowledge on interactions between Yersinia and the inflammasome system, with the goal of integrating these findings within the general framework of inflammasome responses to microbial pathogens.

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Acknowledgments

We would like to thank Sunny Shin and members of the Brodsky and Shin labs for scientific discussion. Work in the Brodsky lab is supported by the NIH-NIAID and a BWF Investigator in the Pathogenesis of Infectious Disease Award.

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Authors and Affiliations

  1. Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19104, USA

    Naomi H. Philip, Erin E. Zwack & Igor E. Brodsky

  2. Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Naomi H. Philip & Igor E. Brodsky

  3. Immunology Graduate Group, Philadelphia, PA, 19104, USA

    Naomi H. Philip

  4. Cell and Molecular Biology Graduate Group, Philadelphia, PA, 19104, USA

    Erin E. Zwack

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  1. Naomi H. Philip
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  2. Erin E. Zwack
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  3. Igor E. Brodsky
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Correspondence to Igor E. Brodsky .

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  1. Department of Biology, Division of Microbiology , Friedrich Alexander University Erlangen/Nuremberg, Erlangen, Germany

    Steffen Backert

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Philip, N.H., Zwack, E.E., Brodsky, I.E. (2016). Activation and Evasion of Inflammasomes by Yersinia . In: Backert, S. (eds) Inflammasome Signaling and Bacterial Infections. Current Topics in Microbiology and Immunology, vol 397. Springer, Cham. https://doi.org/10.1007/978-3-319-41171-2_4

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