Much of what we know about the in vivo function of dendritic cells (DCs) has been derived from Cd11c.DTR mice, in which DCs are conditionally depleted by injection of diphtheria toxin (DT). This study shows that, in addition to causing DC depletion, DT administration unexpectedly results in an early increase (within 24 hours) in blood neutrophils in Cd11c.DTR mice and was associated with improved bacterial clearance in a model of pyelonephritis compared with non-depleted mice. Similarly, early neutrophilia and enhanced bacterial clearance were observed following DT administration in a related mouse line termed Cd11c.DOG mice. Finally, the authors describe another mouse line, termed Cd11c.LuciDTR mice, that was not associated with early neutrophilia (but did develop late neutrophilia) following DT administration. Bacterial clearance was delayed in these mice compared with non-depleted Cd11c.LuciDTR mice. So, the choice of transgenic mouse model for DC depletion may influence experimental results under conditions in which neutrophils may be involved.