|
|
Blood, 29 January 2009, Vol. 113, No. 5, pp. 1045-1052.
Prepublished online as a Blood First Edition Paper on October 29, 2008; DOI 10.1182/blood-2007-10-117861.
 Previous Article | Next Article 
Submitted October 11, 2007
Accepted September 8, 2008
Hematopoietic cell derived interferon controls viral replication and virus induced disease
Philipp A Lang*, Luisa Cervantes-Barragan, Admar Verschoor, Alexander A Navarini, Mike Recher, Marc Pellegrini, Lukas Flatz, Andreas Bergthaler, Kenya Honda, Burkhard Ludewig, Pamela S Ohashi, and Karl S Lang
Institute of Physiology, University of Tubingen, Tubingen, Germany
Research Department, Kantonal Hospital St Gallen, St Gallen, Switzerland
Institute of Experimental Immunology, University Hospital of Zurich, Zurich, Switzerland
Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland
Clinic for Immunology, University Hospital of Zurich, Zurich, Switzerland
Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, Toronto, Ontario, Canada
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
* Corresponding author; email: philipp.lang{at}gmx.net.
Type I interferon (IFN-I) strongly inhibits viral replication and is a crucial factor in the control of a range of virus infections and diseases. Cellular activation through pattern recognition receptors induces interferon-production in a wide variety of hematopoietic and non-hematopoietic cell types, including dendritic cells, fibroblasts, hepatocytes and cells of neuronal origin. The relative contribution of hematopoietic and non hematopoietic cells to the overall interferon response is an important issue which has not been fully addressed. Using irf7-/- and WT bone marrow chimeras we analyzed the contribution of IFN-I from bone marrow derived sources in the control of viral infections and immunopathology in mice. We found that during systemic cytopathic virus infection, hematopoietic cells were essential for production of IFN-I, inhibition of viral spread to peripheral organs and in limiting cell damage. In a model of type I diabetes induced by non-cytopathic virus infection, systemic IFN-I was essential for CD8+ T cell dependent cytotoxicity in pancreatic  -islet cells and induction of diabetes. These data suggest that during systemic viral infection primarily hematopoietic derived IFN-I controls viral replication and viral induced disease.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
|
|
