Functionally relevant neutrophilia in CD11c diphtheria toxin receptor transgenic mice

Nat Methods. 2012 Feb 26;9(4):385-90. doi: 10.1038/nmeth.1905.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11c Antigen / genetics
  • CD11c Antigen / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology
  • Dendritic Cells / pathology
  • Diphtheria Toxin / pharmacology
  • Disease Models, Animal
  • Female
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Immunological
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Pyelonephritis / immunology
  • Pyelonephritis / microbiology
  • Pyelonephritis / pathology
  • Uropathogenic Escherichia coli / immunology
  • Uropathogenic Escherichia coli / physiology

Substances

  • CD11c Antigen
  • Diphtheria Toxin