help button home button Am J Pathol Epitomics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2009.090033 on July 9, 2009

Published online before print July 9, 2009
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2009.090033v1
175/2/510    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jäkel, S.
Right arrow Articles by Voigt, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jäkel, S.
Right arrow Articles by Voigt, A.
(American Journal of Pathology. 2009;175:510-518.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.090033

Differential Interferon Responses Enhance Viral Epitope Generation by Myocardial Immunoproteasomes in Murine Enterovirus Myocarditis

Sandra Jäkel*, Ulrike Kuckelkorn*, Gudrun Szalay{dagger}, Michael Plötz{ddagger}, Kathrin Textoris-Taube*, Elisa Opitz{ddagger}, Karin Klingel{dagger}, Stefan Stevanovic{dagger}, Reinhard Kandolf{dagger}, Katja Kotsch§, Karl Stangl{ddagger}, Peter M. Kloetzel* and Antje Voigt{ddagger}

From the Institute for Biochemistry,* and the Clinic for Immunology,§ Charité-Universitätsmedizin Berlin, Berlin; the Department of Molecular Pathology,{dagger} University Hospital, Tuebingen; and the Clinic for Cardiology and Angiology,{ddagger} Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin; Germany

Murine models of coxsackievirus B3 (CVB3)-induced myocarditis mimic the divergent human disease course of cardiotropic viral infection, with host-specific outcomes ranging from complete recovery in resistant mice to chronic disease in susceptible hosts. To identify susceptibility factors that modulate the course of viral myocarditis, we show that type-I interferon (IFN) responses are considerably impaired in acute CVB3-induced myocarditis in susceptible mice, which have been linked to immunoproteasome (IP) formation. Here we report that in concurrence with distinctive type-I IFN kinetics, myocardial IP formation peaked early after infection in resistant mice and was postponed with maximum IP expression concomitant to massive inflammation and predominant type-II IFN responses in susceptible mice. IP activity is linked to a strong enhancement of antigenic viral peptide presentation. To investigate the impact of myocardial IPs in CVB3-induced myocarditis, we identified two novel CVB3 T cell epitopes, virus capsid protein 2 [285-293] and polymerase 3D [2170-2177]. Analysis of myocardial IPs in CVB3-induced myocarditis revealed that myocardial IP expression resulted in efficient epitope generation. As opposed to the susceptible host, myocardial IP expression at early stages of disease corresponded to enhanced CVB3 epitope generation in the hearts of resistant mice. We propose that this process may precondition the infected heart for adaptive immune responses. In conclusion, type-I IFN-induced myocardial IP activity at early stages coincides with less severe disease manifestation in CVB3-induced myocarditis.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American Society for Investigative Pathology.