IL-1R and inflammasomes mediate early pulmonary protective mechanisms in respiratory brucella abortus infection

M. Soledad Hielpos, Andrea G. Fernández, Juliana Falivene, Iván M.Alonso Paiva, Florencia Muñoz González, Mariana C. Ferrero, Priscila C. Campos, Angelica T. Vieira, Sergio Costa Oliveira, Pablo C. Baldi

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Brucella spp. infection is frequently acquired through contaminated aerosols. The role of interleukin-1 beta (IL-1β) in the early pulmonary response to respiratory Brucella infection is unknown. As shown here, IL-1β levels in lung homogenates and bronchoalveolar lavage fluid (BALF) of mice intratracheally inoculated with B. abortus were increased at 3 and 7 days p.i. At 7 days p.i., pulmonary CFU numbers were higher in IL-1 receptor (IL-1R) knockout (KO) mice than in wild type (WT) mice. At different times p.i. CFU in lungs and BALF were higher in mice lacking some inflammasome components (caspase-1, AIM2, NLRP3) than in WT mice. At 2 days p.i. pulmonary levels of IL-1b and CXCL1 (neutrophils chemoattractant) were lower in caspase-1/11 KO mice. At day 3 p.i., neutrophils counts in BALF were lower in caspase-1/11 KO mice than in WT mice. During in vitro infections, IL-1β secretion was lower in alveolar macrophages from caspase-1/11, NLRP3 or AIM2 KO mice than in WT controls. Similarly, IL-1β production by B. abortus-infected alveolar epithelial cells was reduced by pretreatment with a specific caspase-1 inhibitor. This study shows that IL-1R, probably through IL-1β action, and the NLRP3 and AIM2 inflammasomes are involved in pulmonary innate immune protective mechanisms against respiratory B. abortus infection.

Original languageEnglish (US)
Article number391
JournalFrontiers in Cellular and Infection Microbiology
Volume8
DOIs
StatePublished - 2018
Externally publishedYes

Keywords

  • Brucella abortus
  • IL-1b
  • Inflammasomes
  • Innate immunity
  • Respiratory infection

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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