Publication

Type I IFN-mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection

Journal Paper/Review - Jan 15, 2009

Units
PubMed

Citation
Cervantes-Barragan L, Kalinke U, Züst R, König M, Reizis B, López-Macías C, Thiel V, Ludewig B. Type I IFN-mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection. Journal of immunology (Baltimore, Md. : 1950) 2009; 182:1099-106.
Type
Journal Paper/Review (English)
Journal
Journal of immunology (Baltimore, Md. : 1950) 2009; 182
Publication Date
Jan 15, 2009
Issn Electronic
1550-6606
Pages
1099-106
Brief description/objective

The swift production of type I IFNs is one of the fundamental aspects of innate immune responses against viruses. Plasmacytoid dendritic cell-derived type I IFNs are of prime importance for the initial control of highly cytopathic viruses such as the mouse hepatitis virus (MHV). The aim of this study was to determine the major target cell populations of this first wave of type I IFNs. Generation of bone marrow-chimeric mice expressing the type I IFN receptor (IFNAR) on either hemopoietic or non-bone marrow-derived cells revealed that the early control of MHV depended mainly on IFNAR expression on hemopoietic cells. To establish which cell population responds most efficiently to type I IFNs, mice conditionally deficient for the IFNAR on different leukocyte subsets were infected with MHV. This genetic analysis revealed that IFNAR expression on LysM+ macrophages and CD11c+ dendritic cells was most important for the early containment of MHV within secondary lymphoid organs and to prevent lethal liver disease. This study identifies type I IFN-mediated cross-talk between plasmacytoid dendritic cells on one side and macrophages and conventional dendritic cells on the other, as an essential cellular pathway for the control of fatal cytopathic virus infection.