Crosstalk between Sentinel and Helper Macrophages Permits Neutrophil Migration into Infected Uroepithelium
نویسندگان
چکیده
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(-) 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(-) 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.
منابع مشابه
Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages.
The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C⁺ and Ly6C(-) macrophage-subtypes and neutrophils in the context of urinary tract infection (UTI) with...
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عنوان ژورنال:
- Cell
دوره 156 شماره
صفحات -
تاریخ انتشار 2014