PI3K/Akt signaling pathway modulates influenza virus induced mouse alveolar macrophage polarization to M1/M2b

PLoS One. 2014 Aug 8;9(8):e104506. doi: 10.1371/journal.pone.0104506. eCollection 2014.

Abstract

Macrophages polarized to M1 (pro-inflammation) or M2 (anti-inflammation) phenotypes in response to environmental signals. In this study, we examined the polarization of alveolar macrophage (AM), following induction by different influenza virus strains (ST169 (H1N1), ST602 (H3N2) and HKG9 (H9N2)). Macrophages from other tissues or cell line exert alternative responding pattern, and AM is necessary for investigating the respiratory system. AM polarized toward the M1 phenotype after 4 hours of infection by all three virus strains, and AM to presented M2b phenotype after 8 hours induction, and immunosuppressive phenotype after 24 hours of induction. Protein expression assay showed similar results as the gene expression analysis for phenotype verification. The ELISA assay showed that TNF-α secretion was up-regulated after 4 and 8 hours of infection by influenza viruses, and it returned to basal levels after 24 hours of infection. IL-10 expression was elevated after 8 and 24 hours of infection. Immunofluorescence showed that iNOS expression was up-regulated but not Arg1 expression. Influenza virus notably increased phospho-Akt but not phospho-Erk1/2 or phospho-p38, and the AM polarization pattern have been changed by LY294002 (PI3K inhibitor). In conclusion, our results demonstrate the dynamic polarization of AM induced by influenza viruses, and suggested that PI3K/Akt signaling pathway modulates AM polarization to M1/M2b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H9N2 Subtype / immunology
  • Influenza A virus / immunology*
  • Influenza, Human / immunology
  • Interleukin-10 / immunology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / virology*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / immunology
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / veterinary
  • Phosphatidylinositol 3-Kinases / immunology*
  • Proto-Oncogene Proteins c-akt / immunology*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Nitric Oxide Synthase Type II
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt

Grants and funding

This study was supported by grants from National Natural Science Foundation of China (81301447, 81374040, 30972766, 31170852, 81001322, 81172795), Guangdong Natural Science Foundation (9451503102003499), Specialized Research Fund for the Doctoral Program of Higher Education (20094402110004), State Key Lab of Agriculture Microbiology Open Foundation (AML200910). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.