CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense

被引：22

作者：

Carevic, M. ^{[1
,2
]}

Oez, H. ^{[1
,2
]}

Fuchs, K. ^{[6
]}

Laval, J. ^{[1
,2
]}

Schroth, C. ^{[1
,2
]}

Frey, N. ^{[1
,2
]}

Hector, A. ^{[1
,2
]}

Bilich, T. ^{[1
,2
]}

Haug, M. ^{[3
]}

Schmidt, A. ^{[3
]}

Autenrieth, S. E. ^{[4
]}

Bucher, K. ^{[5
,6
]}

Beer-Hammer, S. ^{[5
,6
]}

Gaggar, A. ^{[9
,10
]}

Kneilling, M. ^{[7
]}

Benarafa, C. ^{[12
]}

Gao, J. L. ^{[11
]}

Murphy, P. M. ^{[11
]}

Schwarz, S. ^{[3
]}

Moepps, B. ^{[8
]}

Hartl, D. ^{[1
,2
]}

机构：

[1] Univ Tubingen, Childrens Hosp, Hoppe Seyler Str 1, DE-72076 Tubingen, Germany

[2] Univ Tubingen, Interdisciplinary Ctr Infect Dis, Hoppe Seyler Str 1, DE-72076 Tubingen, Germany

[3] Univ Tubingen, Dept Med Microbiol, DE-72076 Tubingen, Germany

[4] Univ Tubingen, Dept Internal Med 2, DE-72076 Tubingen, Germany

[5] Univ Tubingen, Dept Pharmacol & Expt Therapy, DE-72076 Tubingen, Germany

[6] Univ Tubingen, Interfac Ctr Pharmacogen & Drug Res, DE-72076 Tubingen, Germany

[7] Univ Tubingen, Dept Preclin Imaging & Radiopharm, Werner Siemens Imaging Ctr, DE-72076 Tubingen, Germany

[8] Univ Ulm, Med Ctr, Inst Pharmacol & Toxicol, D-89069 Ulm, Germany

[9] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[10] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA

[11] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[12] Univ Bern, Theodor Kocher Inst, Bern, Switzerland

来源：

JOURNAL OF INNATE IMMUNITY | 2016年 / 8卷 / 04期

基金：

美国国家卫生研究院;

关键词：

CXCR1; Chemokine receptors; Pseudomonas; Neutrophils; Cystic fibrosis; Toll-like receptor 5; Reactive oxygen species; FIBROSIS LUNG-DISEASE; PSEUDOMONAS-AERUGINOSA INFECTION; CYSTIC-FIBROSIS; CHEMOKINE RECEPTORS; NEUTROPHILS; TLR5; PATHOGENESIS; GCP-2/CXCL6; ACTIVATION; EXPRESSION;

D O I：

10.1159/000444125

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. (C) 2016 S. Karger AG, Basel

引用

页码：362 / 373

页数：12

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