Potential role for alternatively activated macrophages in the secondary bacterial infection during recovery from

Wilbur H Chen1, Franklin R Toapanta, Kari Ann Shirey

  • 1Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA. wchen@medicine.umaryland.edu

Immunology Letters
|November 1, 2011
PubMed
Abstract

Insights

Influenza infection impairs immune defenses, making mice susceptible to secondary bacterial pneumonia. Pulmonary alternatively activated macrophages (AAM) induced by influenza may drive this increased susceptibility.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Pulmonary Medicine

Background:

  • Secondary bacterial infections frequently complicate influenza virus infections.
  • Impaired innate immune defenses post-influenza contribute to heightened susceptibility to bacterial pathogens.
  • Pulmonary alternatively activated macrophages (AAM) are implicated in the hypersusceptibility to secondary bacterial pneumonia.

Purpose of the Study:

  • To investigate the role of pulmonary alternatively activated macrophages (AAM) in the increased susceptibility to secondary bacterial pneumonia following influenza infection.
  • To elucidate the mechanisms of immune regulation during recovery from influenza.

Main Methods:

  • C57BL6 mice were infected with sublethal doses of influenza A virus (PR8) or saline.
  • Following recovery, mice were re-challenged with Streptococcus pneumoniae.
  • Gene expression, flow cytometry, and cytokine responses were analyzed.

Main Results:

  • Mice recovered from influenza (PR8) exhibited a 100-fold increased susceptibility to a lethal Streptococcus pneumoniae challenge compared to naive mice.
  • Pulmonary AAM markers (Arginase-1, FIZZ1, YM1) and associated cytokines (IL-4, IL-13) were upregulated post-influenza.
  • Alveolar macrophages displayed AAM phenotype markers (MGL-1, MHCII) after PR8 infection.
  • Influenza recovery was linked to blunted cytokine responses to TLR ligands.

Conclusions:

  • Pulmonary alternatively activated macrophages (AAM) are induced during influenza infection.
  • These AAM may play a critical role in mediating hypersusceptibility to secondary bacterial pneumonia after influenza.
  • Further research into influenza-induced immune dysregulation is warranted.

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