title: Antigen-presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis.
abstract: Coxsackievirus B3 (CVB3)-infection is a frequent cause of acute myocarditis, which may result in chronic myocarditis and virus persistence. Investigation of the initial immune responses to CVB3 may shed light on the mechanisms that contribute to ongoing disease. DCs, as key professional APCs, were investigated in two MHC-matched hosts: while C57BL/6 mice are resistant to chronic CVB3-myocarditis, the A.BY/SnJ mouse strain exhibits susceptibility. DC maturation and activation were critically impaired in A.BY/SnJ mice, as reflected by the failure of DCs to induce co-stimulatory molecules and cytokine/chemokine responses. MHC class I-restricted antigen presentation via the cross-presentation pathway was also affected in DCs from A.BY/SnJ mice. DC maturation involves the accumulation of DC aggresome-like induced structures (DALISs) and the transient storage of defective ribosomal products (DRiPs). DCs from A.BY/SnJ mice showed permanent DALIS accumulation; the detection of poly-ubiquitinylated CVB3 proteins in these DALISs suggested a limitation in the MHC class I antigenic supply in this host. In conclusion, ongoing chronic disease in A.BY/SnJ mice due to a failure to clear the virus may be attributed to defects in DC maturation/activation and DC MHC class I antigen processing.
authors.affiliation: Clinic for Cardiology and Angiology, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Rahnefeld
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ebstein
authors.forename: Nadine
authors.initials: N
authors.lastname: Albrecht
authors.forename: Elisa
authors.initials: E
authors.lastname: Opitz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuckelkorn
authors.forename: Karl
authors.initials: K
authors.lastname: Stangl
authors.forename: Armin
authors.initials: A
authors.lastname: Rehm
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Antje
authors.initials: A
authors.lastname: Voigt
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000150:complications / Q000276:immunology*; D045142:Cross-Priming; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004770:Enterovirus / Q000276:immunology* / Q000472:pathogenicity; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009205:Myocarditis / Q000209:etiology; D054875:Ubiquitination; D014774:Virulence
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I