Evasion of inflammasome activation by microbial pathogens
Tyler K. Ulland, Polly J. Ferguson, Fayyaz S. Sutterwala
Tyler K. Ulland, Polly J. Ferguson, Fayyaz S. Sutterwala
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Review

Evasion of inflammasome activation by microbial pathogens

Abstract

Activation of the inflammasome occurs in response to infection with a wide array of pathogenic microbes. The inflammasome serves as a platform to activate caspase-1, which results in the subsequent processing and secretion of the proinflammatory cytokines IL-1β and IL-18 and the initiation of an inflammatory cell death pathway termed pyroptosis. Effective inflammasome activation is essential in controlling pathogen replication as well as initiating adaptive immune responses against the offending pathogens. However, a number of pathogens have developed strategies to evade inflammasome activation. In this Review, we discuss these pathogen evasion strategies as well as the potential infectious complications of therapeutic blockade of IL-1 pathways.

Authors

Tyler K. Ulland, Polly J. Ferguson, Fayyaz S. Sutterwala

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Figure 3

Evasion of AIM2 inflammasome activation by intracellular pathogens.

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Evasion of AIM2 inflammasome activation by intracellular pathogens. F. t...
F. tularensis and L. monocytogenes express a number of proteins involved in maintenance of bacterial cell wall integrity. In their absence, increased damage to a subpopulation of bacteria occurs while in the macrophage phagosome, resulting in leakage of bacterial DNA. Once Francisella and Listeria escape into the cytosol of the cell, this DNA is also released into the host cell cytosol, where it interacts with and activates the AIM2 inflammasome. F. tularensis ripA and the gene products of FTL_0325 inhibit MAPK and TLR2 signaling, respectively, and interfere with priming of the AIM2 inflammasome. L. pneumophila secretes the effector molecule into the LCV, where it maintains LCV membrane integrity and prevents Legionella DNA from entering the cytosol and being recognized by AIM2. M. tuberculosis secretes DNA into the cytosol via the ESX-1 secretion system concurrently with an unknown inhibitor of IFN-β and also possibly AIM2.