Abstracts (complete list) - Wissenschaft Online

Stefanie Scheu, Philipp Dresing, Richard M. Locksley
An IFNβ Reporter Mouse Model for the Visualization of the
Initiation of the Type I Interferon Response in vivo
Type I interferons (IFNs) were initially identified on the basis of their antiviral activities.
However, recent studies place these cytokines at the interface between the innate and
adaptive immune system, with additional important roles in bacterial and parasitic
infections and antitumoral and immunomodulatory features. Structurally, type I IFNs
can be grouped into a protein family of multiple IFNα subtypes, encoded by at least 13
different genes in the mouse, and a single IFNβ subtype. The canonical pathway for
IFNα/β production is initiated by the IRF-3 mediated expression of IFNβ leading to a
positive feedback loop via the IFN type I receptor and IRF-7. Although the interferon
produced first in most situations is IFNβ the celltypes responsible for this initial
production remain unclear. To reveal the identity of these IFNβ producers in vitro and in
vivo we created an IFNβ reporter knock in mouse which expresses the enhanced yellow
fluorescent protein (eYFP) from a bicistronic mRNA linked by an IRES to the endogenous
IFNβ message. In vitro experiments with bone marrow derived macrophages (BMDM)
and dendritic cells (BMDDCs) show IFNβ production from distinct cell subpopulations in
response to defined pathogen compounds. The highest frequencies of IFNβ/YFP + cells
were observed in BMDMs after poly(I:C) treatment. This response was already
detectable 4 hours after poly(I:C) stimulation with a peak at 24 hours. A small
population of GMCSF-grown BMDDCs produced IFNβ after poly(I:C), CpG or LPS
treatment whereas FLT3-L cultured B220 + pDCs responded mainly to CpG. Initial in vivo
data show that after poly(I:C) injection IFNβ producing CD11c + cells localized to the
marginal zone and T cell areas of the spleen whereas in lymph nodes accumulations of
IFNβ producing cells could be observed in the subcapsular sinus. Additional data will be
presented validating these IFNβ/YFP reporter mice as a valuable tool for the
visualization and characterization of IFNβ producing cells in vitro and in vivo after
challenge with defined pathogen compounds or in infection models.