IL-1β activation in response to Staphylococcus aureus lung infection requires inflammasome-dependent and independent mechanisms. Academic Article uri icon

Overview

abstract

  • Maintaining balanced levels of IL-1β is extremely important to avoid host tissue damage during infection. Our goal was to understand the mechanisms behind the reduced pathology and decreased bacterial burdens in Ifnlr1-/- mice during lung infection with Staphylococcus aureus. Intranasal infection of Ifnlr1-/- mice with S. aureus led to significantly improved bacterial clearance, survival and decrease of proinflammatory cytokines in the airway including IL-1β. Ifnlr1-/- mice treated with recombinant IL-1β displayed increased bacterial burdens in the airway and lung. IL-1β levels in neutrophils from Ifnlr1-/- infected mice lungs were decreased when compared to neutrophils from WT mice. Mice lacking NLRP3 and caspase-1 had reduced IL-1β levels 4 h after infection, due to reductions or absence of active caspase-1 respectively, but levels at 24 h were comparable to WT infected mice. Ifnlr1-/- infected mice had decreases in both active caspase-1 and neutrophil elastase indicating an important role for the neutrophil serine protease in IL-1β processing. By inhibiting neutrophil elastase, we were able to decrease IL-1β levels by 39% in Nlrp3-/- infected mice when compared to WT mice. These results highlight the crucial role of both proteases in IL-1β processing, via inflammasome-dependent and -independent mechanisms.

publication date

  • August 19, 2018

Research

keywords

  • Caspase 1
  • Inflammasomes
  • Interleukin-1beta
  • Leukocyte Elastase
  • Lung
  • Staphylococcal Infections

Identity

PubMed Central ID

  • PMC6394835

Scopus Document Identifier

  • 85052487087

Digital Object Identifier (DOI)

  • 10.1002/eji.201847556

PubMed ID

  • 30051912

Additional Document Info

volume

  • 48

issue

  • 10