Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium
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Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium. / 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.
in: CELL, Jahrgang 156, Nr. 3, 30.01.2014, S. 456-468.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium
AU - Schiwon, Marzena
AU - Weisheit, Christina
AU - Franken, Lars
AU - Gutweiler, Sebastian
AU - Dixit, Akanksha
AU - Meyer-Schwesinger, Catherine
AU - Pohl, Judith-Mira
AU - Maurice, Nicholas J
AU - Thiebes, Stephanie
AU - Lorenz, Kristina
AU - Quast, Thomas
AU - Fuhrmann, Martin
AU - Baumgarten, Georg
AU - Lohse, Martin J
AU - Opdenakker, Ghislain
AU - Bernhagen, Jürgen
AU - Bucala, Rick
AU - Panzer, Ulf
AU - Kolanus, Waldemar
AU - Gröne, Hermann-Josef
AU - Garbi, Natalio
AU - Kastenmüller, Wolfgang
AU - Knolle, Percy A
AU - Kurts, Christian
AU - Engel, Daniel R
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/1/30
Y1 - 2014/1/30
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens, Ly
KW - Bacterial Infections
KW - Chemokine CXCL2
KW - Female
KW - Immune System Diseases
KW - Kinetics
KW - Leukocyte Disorders
KW - Macrophages
KW - Matrix Metalloproteinase 9
KW - Mice
KW - Neutrophils
KW - Specific Pathogen-Free Organisms
KW - Tumor Necrosis Factor-alpha
KW - Urinary Tract Infections
U2 - 10.1016/j.cell.2014.01.006
DO - 10.1016/j.cell.2014.01.006
M3 - SCORING: Journal article
C2 - 24485454
VL - 156
SP - 456
EP - 468
JO - CELL
JF - CELL
SN - 0092-8674
IS - 3
ER -