Open AccessIFN‐γ production dominates the early human natural killer cell response to Coxsackievirus infection
Author(s) -
Hühn Michael H.,
Hultcrantz Monica,
Lind Katharina,
Ljunggren HansGustaf,
Malmberg KarlJohan,
FlodströmTullberg Malin
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.01056.x
Subject(s) - biology , immunology , immune system , interleukin 12 , interleukin 21 , interferon , cell , peripheral blood mononuclear cell , lymphokine activated killer cell , natural killer cell , janus kinase 3 , human leukocyte antigen , cytotoxic t cell , t cell , antigen , in vitro , biochemistry , genetics
Summary 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 γ (IFN‐γ) 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‐γ production, rather than cytotoxicity, marks the early human NK cell response to CVB3 infection.