title: Defense against influenza A virus infection: essential role of the chemokine system.
abstract: Monocytes/macrophages are highly susceptible to an infection with influenza A virus. After infection, de novo virus protein synthesis is detectable but rapidly interrupted before completion of the first viral replication cycle. Within 24-48 hours the infected monocytes die by apoptosis. Before cell death, infected monocytes initiate a cell-specific immune response. This includes the transcription and subsequent release of TNF-alpha (tumor necrosis factor alpha), IL-1beta (Interleukin 1beta), IL-6, type I inferferons and CC chemokines. Enhanced cytokine mRNA expression is due to a prolonged mRNA stability and an augmented gene transcription. Activation of transcription factors such as NF-kappaB (nuclear factor kappaB) and AP-1 are involved in activation of cytokine mRNA transcription. Infection of monocytes with influenza A virus induces the selective expression of mononuclear leukocyte attracting chemokines, such as MCP-1 (monocyte chemotactic protein 1), MIP-1alpha (macrophage inflammatory protein 1alpha) and RANTES (regulated upon activation, normal T cell expressed and secreted). In striking contrast, the release of the neutrophil-specific chemokines IL-8 (interleukin 8) and GRO-alpha (growth stimulatory activity alpha) is entirely suppressed. This differentially regulated chemokine expression may explain the mononuclear cell infiltrate characteristic for virus-infected tissue. Thus, infection of monocytes/macrophages with influenza A virus primes for a rapid proinflammatory reaction and induces an enhanced immigration of mononuclear cells into infected tissue. Taken together, these mechanisms may prepare the infected host for a fast and virus-specific immune response.
authors.affiliation: Institute of Immunology, Philipps-University, Marburg, Germany. kaufmana@mailer.uni-marburg.de
authors.forename: A
authors.initials: A
authors.lastname: Kaufmann
authors.forename: R
authors.initials: R
authors.lastname: Salentin
authors.forename: R G
authors.initials: RG
authors.lastname: Meyer
authors.forename: D
authors.initials: D
authors.lastname: Bussfeld
authors.forename: C
authors.initials: C
authors.lastname: Pauligk
authors.forename: H
authors.initials: H
authors.lastname: Fesq
authors.forename: P
authors.initials: P
authors.lastname: Hofmann
authors.forename: M
authors.initials: M
authors.lastname: Nain
authors.forename: D
authors.initials: D
authors.lastname: Gemsa
authors.forename: H
authors.initials: H
authors.lastname: Sprenger
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D009000:Monocytes / Q000276:immunology
chemical_list: D018925:Chemokines