Papers by Daniel r. Engel
Infection and Immunity, 2006
Here, we studied their role in UTI using an experimental model induced by transurethral instillat... more Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic Escherichia coli (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b ؉ F4/80 ؉ CD8 ؊ Gr-1 ؊ myeloid subtype. Also, tumor necrosis factor alpha (TNF-␣)-and inducible nitric oxide synthase (iNOS)-producing CD11b INT DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2 ؊/؊ mice did not show reduced clearance of UPEC from the infected bladder. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS-and TNF-␣-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder.
Cell, 2014
The phagocytes of the innate immune system, macrophages and neutrophils, contribute to antibacter... more The phagocytes of the innate immune system, macrophages and neutrophils, contribute to antibacterial defense, but their functional specialization and cooperation is unclear. Here, we report that three distinct phagocyte subsets play highly coordinated roles in bacterial urinary tract infection. Ly6C À macrophages acted as tissue-resident sentinels that attracted circulating neutrophils and Ly6C + macrophages. Such Ly6C + macrophages played a previously undescribed helper role: once recruited to the site of infection, they produced the cytokine TNF, which caused Ly6C À macrophages to secrete CXCL2. This chemokine activated matrix metalloproteinase-9 in neutrophils, allowing their entry into the uroepithelium to combat the bacteria. In summary, the sentinel macrophages elicit the powerful antibacterial functions of neutrophils only after confirmation by the helper macrophages, reminiscent of the licensing role of helper T cells in antiviral adaptive immunity. These findings identify helper macrophages and TNF as critical regulators in innate immunity against bacterial infections in epithelia.
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Papers by Daniel r. Engel