Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response

J Leukoc Biol. 1997 Apr;61(4):408-14. doi: 10.1002/jlb.61.4.408.


Among leukocytes, only monocytes and macrophages were found to be highly susceptible to an infection by influenza A virus. After infection, de novo viral protein synthesis was initiated but then interrupted after 4-6 h. Most macrophages died by apoptosis within 25-30 h. Before cell death, however, macrophages responded to influenza A virus with a high cytokine gene transcription and subsequent release of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, interferon (IFN)-alpha/beta, and CC-chemokines. The basic mechanisms of virus-induced cytokine expression are still unknown and appear to involve transcription factors such as nuclear factor-kappaB and AP-1 which, however, were only activated for 2 h and declined below control values thereafter. After influenza A virus infection, only the mononuclear cell attracting CC-chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES were produced while the prototype neutrophil CXC-chemoattractants IL-8 and GRO-alpha were entirely suppressed. This selective induction of CC-chemokines may explain the preferential influx of mononuclear leukocytes into virus-infected tissue. Our data show that monocytes and macrophages represent a primary target for an influenza A virus infection. Thus, the mononuclear phagocyte response leads to a rapid proinflammatory reaction and an enhanced immigration of mononuclear leukocytes, which may condition the infected host for the subsequent virus antigen-specific defense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cells, Cultured
  • Chemotaxis, Leukocyte
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • Disease Susceptibility
  • Fluorescent Antibody Technique
  • Humans
  • Influenza A virus*
  • Influenza, Human / immunology*
  • Influenza, Human / metabolism
  • Influenza, Human / pathology
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology*
  • Phagocytes / immunology*
  • Phagocytes / metabolism
  • Phagocytes / virology*
  • Up-Regulation / drug effects
  • Viral Proteins / biosynthesis


  • Cytokines
  • Viral Proteins