Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages

Nat Commun. 2013;4:2106. doi: 10.1038/ncomms3106.

Abstract

While the presence of airway bacteria is known to be associated with improved immunity against influenza virus, the mechanism by which endogenous microbiota influence antiviral immunity remains unclear. Here we show that specific pathogen-free mice are more sensitive to influenza-mediated death than mice living in a natural environment. Priming with Toll-like receptor 2-ligand(+) Staphylococcus aureus, which commonly colonizes the upper respiratory mucosa, significantly attenuates influenza-mediated lung immune injury. Toll-like receptor 2 deficiency or alveolar macrophage depletion abolishes this protection. S. aureus priming recruits peripheral CCR2(+)CD11b(+) monocytes into the alveoli that polarize to M2 alveolar macrophages in an environment created by Toll-like receptor 2 signalling. M2 alveolar macrophages inhibit influenza-mediated lethal inflammation via anti-inflammatory cytokines and inhibitory ligands. Our results suggest a previously undescribed mechanism by which the airway microbiota may protect against influenza-mediated lethal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / complications
  • Acute Lung Injury / immunology*
  • Acute Lung Injury / microbiology*
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control
  • Animals
  • CD11b Antigen / metabolism
  • Cell Count
  • Cell Polarity
  • Colony Count, Microbial
  • Humans
  • Inflammation / pathology
  • Influenza, Human / complications
  • Influenza, Human / immunology*
  • Influenza, Human / microbiology*
  • Influenza, Human / pathology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • Orthomyxoviridae Infections / complications
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / microbiology
  • Orthomyxoviridae Infections / pathology
  • Staphylococcus aureus / growth & development*
  • Survival Analysis
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / metabolism

Substances

  • CD11b Antigen
  • Toll-Like Receptor 2