Guanylate-binding proteins at the crossroad of noncanonical inflammasome activation during bacterial infections

Marco Túlio R. Gomes, Daiane M. Cerqueira, Erika S. Guimarães, Priscila C. Campos, Sergio C. Oliveira

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

The immune system is armed with a broad range of receptors to detect and initiate the elimination of bacterial pathogens. Inflammasomes are molecular platforms that sense a diverse range of microbial insults to develop appropriate host response. In that context, noncanonical inflammasome arose as a sensor for Gram-negative bacteria-derived LPS leading to the control of infections. This review describes the role of caspase-11/gasdermin-D-dependent immune response against Gram-negative bacteria and presents an overview of guanylate-binding proteins (GBPs) at the interface of noncanonical inflammasome activation. Indeed, caspase-11 acts as a receptor for LPS and this interaction elicits caspase-11 autoproteolysis that is required for its optimal catalytic activity. Gasdermin-D is cleaved by activated caspase-11 generating an N-terminal domain that is inserted into the plasmatic membrane to form pores that induce pyroptosis, a cell death program involved in intracellular bacteria elimination. This mechanism also promotes IL-1β release and potassium efflux that connects caspase-11 to NLRP3 activation. Furthermore, GBPs display many features to allow LPS recognition by caspase-11, initiating the noncanonical inflammasome response prompting the immune system to control bacterial infections. In this review, we discuss the recent findings and nuances related to this mechanism and its biological functions.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalJournal of Leukocyte Biology
Volume106
Issue number3
DOIs
StatePublished - Sep 1 2019
Externally publishedYes

Keywords

  • caspase-11
  • gasdermin-D
  • K+ efflux
  • NLRP3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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