title: The activating receptor NKG2D of natural killer cells promotes resistance against enterovirus-mediated inflammatory cardiomyopathy.
abstract: In enterovirus-induced cardiomyopathy, information regarding the detailed impact of natural killer (NK) cells on the outcome of the disease is limited. We therefore hypothesized that NK cells and certain NK cell receptors determine the different outcome of coxsackievirus B3 (CVB3) myocarditis. Here, we demonstrate in murine models that resistance to chronic CVB3 myocarditis in immunocompetent C57BL/6 mice is characterized by significantly more mature CD11b(high) NK cells, the presence of NKG2D on NK cells, and enhanced NKG2D-dependent cytotoxicity compared to CVB3-susceptible A.BY/SnJ mice. The highly protective role of NKG2D in myocarditis was further proven by in vivo neutralization of NKG2D as well as in NKG2D-deficient mice but was shown to be independent of CD8(+) T-cell-dependent immunity. Moreover, the adoptive transfer of immunocompetent C57BL/6 NK cells pre- (day -1) as well as post-infectionem (day +2) displayed the potential to prevent permissive A.BY/SnJ mice from a progressive outcome of CVB3 myocarditis reflected by significantly improved cardiopathology and heart function. Altogether, our results provide firm evidence for a protective role of NKG2D-activated NK cells in CVB3 myocarditis leading to an effective virus clearance, thus offering novel therapeutic options in the treatment of virus-induced myocarditis.
authors.affiliation: Department of Molecular Pathology, University Hospital Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Cornelia
authors.initials: C
authors.lastname: Fabritius
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.forename: Katrin
authors.initials: K
authors.lastname: Göldner
authors.forename: Diana
authors.initials: D
authors.lastname: Stauch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Nicole
authors.initials: N
authors.lastname: Ettischer
authors.forename: Sabine
authors.initials: S
authors.lastname: Gahlen
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Susanne
authors.initials: S
authors.lastname: Ebner
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Makrigiannis
authors.forename: Simon
authors.initials: S
authors.lastname: Bélanger
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.forename: Bojan
authors.initials: B
authors.lastname: Polić
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: Katja
authors.initials: K
authors.lastname: Kotsch
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D009202:Cardiomyopathies / Q000276:immunology / Q000473:pathology / Q000821:virology*; D003384:Coxsackievirus Infections / Q000517:prevention & control; D004770:Enterovirus / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000209:etiology / Q000276:immunology; D009206:Myocardium / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism*
chemical_list: D055655:NK Cell Lectin-Like Receptor Subfamily K
keywords: NKG2D; natural killer cells; virus-induced cardiomyopathy