The Effects of Macrophage Polarity on Influenza Virus Replication and Innate Immune Responses

Isabelle Dutry Jibin Li

doi:10.4172/2155-9899.1000297

Abstract

Different pathways of macrophage differentiation and activation lead to diverse macrophage phenotypes including expression of cell surface molecules, cytokine secretion and transcription profiles. Here we investigated in vitro the impact of inflammatory or anti-inflammatory polarization of human primary macrophages on their susceptibility to Influenza A virus infection and characterised innate immune responses in infected cells. M2 M-CSF+IL4 macrophages showed greater susceptibility to influenza A infection than M1 GM-CSF+interferon (IFN)γ macrophages.

Highlights

Seasonal influenza A viruses are respiratory pathogens causing annual epidemics, typically causing mild illnesses but significant morbidity at the extremes of age
Cells were seeded on coverslips into 24-well tissue culture plates at 0.35 × 106 cells/well for differentiation in RPMI 1640 medium supplemented with 100 U/mL penicillin, 100 μg/mL streptomycin and either 5% of autologous plasma or in RPMI 1640 medium supplemented with 10% heatinactivated FBS, 1% non-essential amino-acids, 4 mM L-glutamine, 1 mM sodium pyruvate, 100 U/mL penicillin, 100 μg/mL streptomycin and 20 μM β2-mercaptoethanol and 50 ng/mL of Macrophage-Colony Stimulating Factor (M-CSF) or Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)
Influenza virus protein expression was detected by immunofluorescence staining for viral proteins in six subpopulations of macrophages (Figure 1A and 1B) at 3, 6 and 24 hours after infection at comparable Multiplicity of Infection (MOI) (MOI=2) with pH1N1, H9N2/G1 or H5N1 virus

Summary

Introduction

Seasonal influenza A viruses are respiratory pathogens causing annual epidemics, typically causing mild illnesses but significant morbidity at the extremes of age. Novel influenza viruses emerge at unpredictable intervals leading to pandemics associated with more widespread and sometimes severe disease. The biological basis for severity of influenza disease remains unclear though it is recognized that the interplay between the influenza viruses and the host immune responses contribute to viral pathogenesis. Macrophages are activated and actively phagocytose infected cells limiting viral spread. Their activation is associated with expression of multiple cytokines and chemokines to orchestrate downstream host cellular defences

Methods

Results

Conclusion