Abstracts (complete list) - Wissenschaft Online

Luisa Cervantes-Barragan, Ulrich Kalinke, Roland Züst, Constantino Lopez-Macias,
Volker Thiel, Burkhard Ludewig
Activation of myeloid cells through plasmacytoid dendritic
cell-derived type I interferon secures control of murine
coronavirus infection
The secretion of type I interferons (IFN) is one of the fundamental aspects of the innate
immune response against viruses. However, the role of type I IFNs in the pathogenesis
of coronavirus infections has not yet been fully clarified, neither its importance for
particular coronavirus infected cell populations. We have shown recently that
plasmacytoid dendritic cell derived type I interferons (IFNs) are of prime importance for
the initial control of mouse hepatitis virus (MHV) infection (Cervantes-Barragan Blood.
2007 109:1131-7). In the present study, we have determined the major target cell
populations of type I IFNs. To this end, we have first generated a series of chimeric
mice expressing the type I interferon receptor (IFNAR) either on hematopoietic or nonbone
marrow-derived cells. Early control of MHV depended mainly on IFNAR expression
on hematopoietic cells. To establish which leukocyte subset responds most efficiently to
type I IFN, mice conditionally deficient for the type I interferon receptor (IFNAR) on
different leukocyte subsets were infected with MHV. This genetic analysis revealed that
IFNAR expression on macrophages/neutrophils and dendritic cells is of prime
importance for the early containment of MHV within secondary lymphoid organs, while
IFN activity on B cells or T cells is not required for the clearance of MHV infection. Taken
together, our results indicate that the protection of macrophages/neutrophils and
CD11c-positive dendritic cells through type I IFN is essential for the control of murine
coronavirus infection.