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Cell. 2014 Jan 30;156(3):456-68. doi: 10.1016/j.cell.2014.01.006.

Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium.

Author information

1
Institute of Experimental Immunology, University Clinic of Bonn, 53127 Bonn, Germany.
2
Institute of Experimental Immunology, University Clinic of Bonn, 53127 Bonn, Germany; Clinic for Anesthesiology, University Clinic of Bonn, 53127 Bonn, Germany.
3
Medizinische Klinik III, University Clinic Hamburg Eppendorf, 20246 Hamburg, Germany.
4
Institute of Pharmacology and Toxicology, University of Würzburg, 97078 Würzburg, Germany.
5
Life and Medical Sciences Institute, Friedrich-Wilhelms-Universität, 53115 Bonn, Germany.
6
German Center for Neurodegenerative Diseases (DZNE), 53125 Bonn, Germany.
7
Clinic for Anesthesiology, University Clinic of Bonn, 53127 Bonn, Germany.
8
Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, 3000 KU Leuven, Belgium.
9
Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, 52062 Aachen, Germany.
10
Yale University School of Medicine, New Haven, CT 06510, USA.
11
Cellular and Molecular Pathology, German Cancer Research Center Heidelberg, 69120 Heidelberg, Germany.
12
Institute of Experimental Immunology, University Clinic of Bonn, 53127 Bonn, Germany. Electronic address: ckurts@web.de.
13
Institute of Experimental Immunology, University Clinic of Bonn, 53127 Bonn, Germany. Electronic address: daniel.robert.engel@gmail.com.

Abstract

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.

PMID:
24485454
PMCID:
PMC4258064
DOI:
10.1016/j.cell.2014.01.006
[Indexed for MEDLINE]
Free PMC Article

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