title: IFN-gamma production dominates the early human natural killer cell response to Coxsackievirus infection.
abstract: Coxsackieviruses (CV) are important human pathogens that have been implicated in the pathogenesis of several diseases, including myocarditis and pancreatitis. How the human immune system recognizes and controls CV infections is not well understood. Studies in mice suggest that natural killer (NK) cells play a critical role in viral clearance and host survival, but the mechanism(s) by which human NK cells may contribute to the host anti-CV defence has not been investigated. Here we show that CVB3 infection markedly reduces HLA class I cell surface expression but does not increase the expression of the activating NK cell receptor ligands MICA/B and ULBP1-3 on human cells. We also demonstrate that the lowered target cell HLA class I surface expression does not correlate with an increased susceptibility to NK cell-mediated killing. However, NK cells responded with a robust production of interferon gamma (IFN-gamma) when peripheral blood mononuclear cells were cocultured with infected cells. In summary, this study shows that CVB3 interferes with the expression of NK cell receptor ligands on infected cells and indicates that IFN-gamma production, rather than cytotoxicity, marks the early human NK cell response to CVB3 infection.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hühn
authors.forename: Monica
authors.initials: M
authors.lastname: Hultcrantz
authors.forename: Katharina
authors.initials: K
authors.lastname: Lind
authors.forename: Hans-Gustaf
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: Karl-Johan
authors.initials: KJ
authors.lastname: Malmberg
authors.forename: Malin
authors.initials: M
authors.lastname: Flodström-Tullberg
mesh_terms: D036022:Capsid Proteins / Q000032:analysis; D003384:Coxsackievirus Infections / Q000276:immunology*; D015536:Down-Regulation; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008024:Ligands; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D011971:Receptors, Immunologic; D007371:Interferon-gamma