{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:26:42Z","timestamp":1791188802317,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cystic fibrosis (CF) lung disease is characterized by infection with Pseudomonas aeruginosa and a sustained accumulation of neutrophils. In this study, we analyzed 1) the expression of MyD88-dependent TLRs on circulating and airway neutrophils in P. aeruginosa-infected CF patients, P. aeruginosa-infected non-CF bronchiectasis patients, and noninfected healthy control subjects and 2) studied the regulation of TLR expression and functionality on neutrophils in vitro. TLR2, TLR4, TLR5, and TLR9 expression was increased on airway neutrophils compared with circulating neutrophils in CF and bronchiectasis patients. On airway neutrophils, TLR5 was the only TLR that was significantly higher expressed in CF patients compared with bronchiectasis patients and healthy controls. Studies using confocal microscopy and flow cytometry revealed that TLR5 was stored intracellularly in neutrophils and was mobilized to the cell surface in a protein synthesis-independent manner through protein kinase C activation or after stimulation with TLR ligands and cytokines characteristic of the CF airway microenvironment. The most potent stimulator of TLR5 expression was the bacterial lipoprotein Pam3CSK4. Ab-blocking experiments revealed that the effect of Pam3CSK4 was mediated through cooperation of TLR1 and TLR2 signaling. TLR5 activation enhanced the phagocytic capacity and the respiratory burst activity of neutrophils, which was mediated, at least partially, via a stimulation of IL-8 production and CXCR1 signaling. This study demonstrates a novel mechanism of TLR regulation in neutrophils and suggests a critical role for TLR5 in neutrophil-P. aeruginosa interactions in CF lung disease.<\/jats:p>","DOI":"10.4049\/jimmunol.181.4.2753","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:08:31Z","timestamp":1397848111000},"page":"2753-2763","source":"Crossref","is-referenced-by-count":81,"title":["TLR Expression on Neutrophils at the Pulmonary Site of Infection: TLR1\/TLR2-Mediated Up-Regulation of TLR5 Expression in Cystic Fibrosis Lung Disease"],"prefix":"10.1093","volume":"181","author":[{"given":"Barbara","family":"Koller","sequence":"first","affiliation":[{"name":"Children\u2032s Hospital of the Ludwig-Maximilians-University , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kappler","sequence":"additional","affiliation":[{"name":"Children\u2032s Hospital of the Ludwig-Maximilians-University , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Latzin","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Gaggar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Department of Physiology\/Biophysics, University of Alabama , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Children\u2032s Hospital of the Ludwig-Maximilians-University , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherkin","family":"Takyar","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Yale University School of Medicine , New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kormann","sequence":"additional","affiliation":[{"name":"Children\u2032s Hospital of the Ludwig-Maximilians-University , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kabesch","sequence":"additional","affiliation":[{"name":"Children\u2032s Hospital of the Ludwig-Maximilians-University , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Roos","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam , Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Griese","sequence":"additional","affiliation":[{"name":"Children\u2032s Hospital of the Ludwig-Maximilians-University , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Hartl","sequence":"additional","affiliation":[{"name":"Children\u2032s Hospital of the Ludwig-Maximilians-University , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,8,15]]},"reference":[{"key":"2026012806193117800_R1","first-page":"137","article-title":"Current understanding of the inflammatory process in cystic fibrosis: onset and etiology","volume-title":"Pediatr. 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