Functionally relevant neutrophilia in CD11c diphtheria toxin receptor transgenic mice.

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.

Kidney dendritic cells induce innate immunity against bacterial pyelonephritis.

Dendritic cells (DCs) are the most abundant immune cells in the kidney and form an intricate network in the tubulointerstitium, suggesting that they may play an important role in interstitial infections such as pyelonephritis. Here, we optimized a murine pyelonephritis model by instilling uropathogenic Escherichia coli two times at a 3-hour interval, which produced an infection rate of 84%. By 3 hours after the second instillation, resident kidney DCs began secreting the chemokine CXCL2, which recruits neutrophilic granulocytes. During the time studied, DCs remained responsible for most of the CXCL2 production. Neutrophils began infiltrating the kidney 3 hours after the second instillation and phagocytozed bacteria. Macrophages followed 3 hours later and contributed much less to both CXCL2 production and bacterial phagocytosis. To investigate whether DCs recruit neutrophils into the kidney for antibacterial defense, we used CD11c.DTR mice allowing conditional depletion of CD11c(+) dendritic cells. The absence of CD11c(+) DCs markedly delayed neutrophil recruitment and bacterial clearance. In conclusion, these findings suggest that the tubulointerstitial dendritic cell network serves an innate immune sentinel function against bacterial pyelonephritis.