title: CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense.
abstract: 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.
authors.affiliation: Children's Hospital and Interdisciplinary Center for Infectious Diseases, University of Tx00FC;bingen, Tx00FC;bingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Carevic
authors.forename: H
authors.initials: H
authors.lastname: Öz
authors.forename: K
authors.initials: K
authors.lastname: Fuchs
authors.forename: J
authors.initials: J
authors.lastname: Laval
authors.forename: C
authors.initials: C
authors.lastname: Schroth
authors.forename: N
authors.initials: N
authors.lastname: Frey
authors.forename: A
authors.initials: A
authors.lastname: Hector
authors.forename: T
authors.initials: T
authors.lastname: Bilich
authors.forename: M
authors.initials: M
authors.lastname: Haug
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: S E
authors.initials: SE
authors.lastname: Autenrieth
authors.forename: K
authors.initials: K
authors.lastname: Bucher
authors.forename: S
authors.initials: S
authors.lastname: Beer-Hammer
authors.forename: A
authors.initials: A
authors.lastname: Gaggar
authors.forename: M
authors.initials: M
authors.lastname: Kneilling
authors.forename: C
authors.initials: C
authors.lastname: Benarafa
authors.forename: J L
authors.initials: JL
authors.lastname: Gao
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
authors.forename: S
authors.initials: S
authors.lastname: Schwarz
authors.forename: B
authors.initials: B
authors.lastname: Moepps
authors.forename: D
authors.initials: D
authors.lastname: Hartl
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000276:immunology / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D017382:Reactive Oxygen Species; D023062:Receptors, Interleukin-8A; D051198:Toll-Like Receptor 5