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
Published February 2, 2015
Citation Information: J Clin Invest. 2015;125(2):469-477. https://doi.org/10.1172/JCI75254.
View: Text | PDF
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

×

Figure 1

Schematic of AIM2, NLRP1B, NLRP3, and NLRC4 inflammasomes.

Options: View larger image (or click on image) Download as PowerPoint
Schematic of AIM2, NLRP1B, NLRP3, and NLRC4 inflammasomes. (A) The AIM2 ...
(A) The AIM2 inflammasome detects the presence of cytosolic dsDNA via its HIN200 domain. AIM2 then recruits ASC through its N-terminal PYD, which recruits caspase-1 via its CARD domain. (B) B. anthracis lethal toxin and T. gondii can induce the activation of the NLRP1B inflammasome. Mouse NLRP1B does not possess a functional N-terminal PYD that is found in human NLRP1; thus, caspase-1 is proposed to interact with its C-terminal CARD. (C) A diverse array of agonists can activate the NLRP3 inflammasome; it is thought that they ultimately lead to mitochondrial dysfunction, resulting in mtDNA and cardiolipin interactions with NLRP3, which leads to its activation. NLRP3 interacts with ASC through an N-terminal PYD, which then recruits caspase-1. (D) NAIP1, NAIP2, and NAIP5/6 bind to the T3SS needle and rod proteins and bacterial flagellin, respectively. The NAIP proteins in turn activate the NLRC4 inflammasome. FIIND, domain with function to find; NACHT, nucleotide-binding and oligomerization domain; LRR, leucine-rich repeats; BIR, baculovirus IAP repeat domain; HIN200; HIN200 domain.