Brucella abortus nitric oxide metabolite regulates inflammasome activation and IL-1β secretion in murine macrophages

Priscila Carneiro Campos, Marco Túlio Ribeiro Gomes, Fábio Antônio Vitarelli Marinho, Erika Sousa Guimarães, Mariza Gabriela Faleiro de Moura Lodi Cruz, Sergio Costa Oliveira

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

NLRP3 inflammasome is a protein complex crucial to caspase-1 activation and IL-1β and IL-18 maturation. This receptor participates in innate immune responses to different pathogens, including the bacteria of genus Brucella. Our group recently demonstrated that Brucella abortus-induced IL-1β secretion involves NLRP3 inflammasome and it is partially dependent on mitochondrial ROS production. However, other factors could be involved, such as P2X7-dependent potassium efflux, membrane destabilization, and cathepsin release. Moreover, there is increasing evidence that nitric oxide acts as a modulator of NLRP3 inflammasome. The aim of this study was to unravel the mechanism of NLRP3 inflammasome activation induced by B. abortus, as well as the involvement of bacterial nitric oxide (NO) as a modulator of this inflammasome pathway. We demonstrated that NO produced by B. abortus can be used by the bacteria to modulate IL-1β secretion in infected murine macrophages. Additionally, our results suggest that B. abortus-induced IL-1β secretion depends on a P2X7-independent potassium efflux, lysosomal acidification, cathepsin release, mechanisms clearly associated to NLRP3 inflammasome. In summary, our results help to elucidate the molecular mechanisms of NLRP3 activation and regulation during an intracellular bacterial infection.

Original languageEnglish (US)
Pages (from-to)1023-1037
Number of pages15
JournalEuropean Journal of Immunology
Volume49
Issue number7
DOIs
StatePublished - Jul 2019
Externally publishedYes

Keywords

  • Brucella abortus
  • immune evasion
  • nitric oxide
  • NLRP3 inflammasome
  • ΔnarG mutant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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