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Title: Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium
Authors: Schiwon, Marzena ×
Weisheit, Christina
Franken, Lars
Gutweiler, Sebastian
Dixit, Akanksha
Meyer-Schwesinger, Catherine
Pohl, Judith-Mira
Maurice, Nicholas J
Thiebes, Stephanie
Lorenz, Kristina
Quast, Thomas
Fuhrmann, Martin
Baumgarten, Georg
Lohse, Martin J
Opdenakker, Ghislain
Bernhagen, Jürgen
Bucala, Rick
Panzer, Ulf
Kolanus, Waldemar
Gröne, Hermann-Josef
Garbi, Natalio
Kastenmüller, Wolfgang
Knolle, Percy A
Kurts, Christian
Engel, Daniel R #
Issue Date: Jan-2014
Publisher: MIT Press
Series Title: Cell vol:156 issue:3 pages:456-68
Article number: 10.1016/j.cell.2014.01.006
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.
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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