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Highly pathogenic avian influenza viruses inhibit effective immune responses of human blood-derived macrophages

Judith Friesenhagen1, Yvonne Boergeling, Eike Hrincius

  • 1Institute of Immunology, University of Muenster, Muenster, Germany.

Journal of Leukocyte Biology
|March 24, 2012
PubMed

Insights

High pathogenic avian influenza viruses (HPAIVs) evade early immune responses by suppressing macrophage inflammatory cytokine and inflammasome activation. This immune evasion facilitates virus spread and systemic disease progression.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Systemic infections with highly pathogenic avian influenza viruses (HPAIVs), like H5N1, trigger cytokine storms and sepsis.
  • Human monocyte-derived macrophages play a crucial role in the immune response to viral infections.

Purpose of the Study:

  • To investigate the role of human monocyte-derived macrophages in the immune response to different influenza virus strains, particularly HPAIVs.
  • To understand how HPAIVs might evade the host's initial innate immune defenses.

Main Methods:

  • Macrophages were infected with low pathogenic H1N1 (PR8) and highly pathogenic H7N7 (FPV) and H5N1 (KAN-1) influenza virus subtypes.
  • Transcriptome analysis was performed to assess the innate immune response.
  • Inflammasome activation and viral protein M2 expression were evaluated.

Main Results:

  • Macrophages were nonpermissive for influenza virus replication.
  • Infection with HPAIVs (H5N1, H7N7) led to an attenuated innate immune response, with significantly reduced induction of inflammatory cytokines and type I IFNs.
  • Inflammasome activation was impaired in HPAIV-infected macrophages, correlating with suppressed viral M2 protein expression.

Conclusions:

  • HPAIVs employ a strategy to evade initial macrophage inflammatory responses, characterized by suppressed cytokine and inflammasome activation.
  • This immune evasion mechanism likely facilitates virus spreading and progression to severe systemic disease.

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