title: Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response.
abstract: 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.
authors.affiliation: Institute of Immunology, Philipps University, Marburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hofmann
authors.forename: H
authors.initials: H
authors.lastname: Sprenger
authors.forename: A
authors.initials: A
authors.lastname: Kaufmann
authors.forename: A
authors.initials: A
authors.lastname: Bender
authors.forename: C
authors.initials: C
authors.lastname: Hasse
authors.forename: M
authors.initials: M
authors.lastname: Nain
authors.forename: D
authors.initials: D
authors.lastname: Gemsa
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004198:Disease Susceptibility; D005455:Fluorescent Antibody Technique; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015854:Up-Regulation / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D014764:Viral Proteins