Transgenic mice expressing the diphtheria toxin receptor (DTR) in specific cell types are key tools for functional studies in several biological systems. B6.FVB-Tg(Itgax-DTR/EGFP)57Lan/J (CD11c.DTR) and B6.Cg-Tg(Itgax-DTR/OVA/EGFP) 1Gjh/Crl (CD11c.DOG) mice express the DTR in CD11c+ cells, allowing conditional depletion of dendritic cells. We report that dendritic-cell depletion in these models caused polymorphonuclear neutrophil (PMN) release from the bone marrow, which caused chemokine-dependent neutrophilia after 6-24 h and increased bacterial clearance in a mouse pyelonephritis model. We present a transgenic mouse line, B6.Cg-Tg(Itgax-EGFP-CRE-DTR-LUC)2Gjh/Crl (CD11c.LuciDTR), which is unaffected by early neutrophilia. However, CD11c.LuciDTR and CD11c.DTR mice showed late neutrophilia 72 h after dendritic cell depletion, which was independent of PMN release and possibly resulted from increased granulopoiesis. Thus, the time point of dendritic cell depletion and the choice of DTR transgenic mouse line must be considered in experimental settings where neutrophils may be involved.
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We thank S. Jung for constructive discussions and correcting the manuscript, B. Schumak (University of Bonn) for providing CD11c.DOG mice, G. Kublbeck and S. Schmidt for assistance in the generation of CD11c.LuciDTR mice. We acknowledge support by the Central Animal Facilities of the Medical Faculty Bonn and the Flow Cytometry Core Facility at the Institutes of Molecular Medicine and Experimental Immunology Bonn. This work was supported by the Deutsche Forschungsgemeinschaft (Ku1038/5 and SFBTR57TP10 to C.K.) and EU Project NoE-MUGEN (LSHG-CT-2005-005203 to G.H.).