Orchestrating an Attack

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Science  21 Feb 2014:
Vol. 343, Issue 6173, pp. 817
DOI: 10.1126/science.343.6173.817-b

Urinary tract infections (UTIs) persist if the innate immune system fails to clear the bacteria. Immune defense against UTIs requires neutrophils, macrophages, and the cytokines they secrete; however, how they all work together is unclear. Using a murine model of UTI, Schiwon et al. found that neutrophils are the key antibacterial effectors in UTI but that neutrophil migration was regulated by two functionally distinct macrophage subsets: sentinel macrophages resident in the bladder and helper macrophages that need to be recruited from the circulation. The sentinel macrophages sensed the infection and produced chemokines to recruit neutrophils and helper macrophages. Helper macrophages did not directly combat bacteria like neutrophils, but did produce the cytokine tumor necrosis factor as a “helper signal,” which allowed the sentinel macrophages to produce the chemokine CXCL2. CXCL2 in turn induced the secretion of matrix metalloproteinase-9, which allowed neutrophils to enter the uroepithelium to combat the bacteria. Thus, the antibacterial phagocyte response is not simply a disorganized tissue invasion of neutrophils and macrophages that clear the bacteria by eating them, but instead a highly coordinated process involving the exchange of information between three phagocyte subsets with distinct immunological tasks.

Cell 156, 456 (2014).

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