a fluorescence reporter model defines “tip-dcs” as the cellular source of interferon β in murine listeriosis荧光记者模型定义u201ctip-dcsu201d干扰素β细胞来源的小鼠李氏杆菌病.pdfVIP

A Fluorescence Reporter Model Defines ‘‘Tip-DCs’’ as the Cellular Source of Interferon b in Murine Listeriosis Philipp Dresing, Stephanie Borkens, Magdalena Kocur, Sonja Kropp, Stefanie Scheu* ¨ ¨ Institute of Medical Microbiology and Hospital Hygiene, University of Dusseldorf, Dusseldorf, Germany Abstract Production of type I interferons, consisting mainly of multiple IFNa subtypes and IFNb, represents an essential part of the innate immune defense against invading pathogens. While in most situations, namely viral infections, this class of cytokines is indispensable for host survival they mediate a detrimental effect during infection with L. monocytogenes by rendering macrophages insensitive towards IFNc signalling which leads to a lethal bacterial pathology in mice. Due to a lack of suitable analytic tools the precise identity of the cell population responsible for type I IFN production remains ill- defined and so far these cells have been described to be macrophages. As in general IFNb is the first type I interferon to be produced, we took advantage of an IFNb fluorescence reporter-knockin mouse model in which YFP is expressed from a bicistronic mRNA linked by an IRES to the endogenous ifnb mRNA to assess the IFNb production on a single cell level in situ. Our results showed highest frequencies and absolute numbers of IFNb+ cells in the spleen 24 h after infection with L. monocytogenes where they were located predominately in the white pulp within the foci of infection. Detailed FACS surface marker analyses, intracellular cytokine stainings and T cell proliferation assays revealed that the IFNb+ cells were a phenotypically and functionally further specialized subpopulation of TNF and iNOS producing DCs (Tip-DCs) which are known to be essen