{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:26:47Z","timestamp":1791268007224,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"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":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pseudomonas aeruginosa persists in patients with cystic fibrosis (CF) and drives CF lung disease progression. P. aeruginosa potently activates the innate immune system, mainly mediated through pathogen-associated molecular patterns, such as flagellin. However, the host is unable to eradicate this flagellated bacterium efficiently. The underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells generated in cancer and proinflammatory microenvironments and are capable of suppressing T cell responses. We hypothesized that P. aeruginosa induces MDSCs to escape T cell immunity. In this article, we demonstrate that granulocytic MDSCs accumulate in CF patients chronically infected with P. aeruginosa and correlate with CF lung disease activity. Flagellated P. aeruginosa culture supernatants induced the generation of MDSCs, an effect that was 1) dose-dependently mimicked by purified flagellin protein, 2) significantly reduced using flagellin-deficient P. aeruginosa bacteria, and 3) corresponded to TLR5 expression on MDSCs in vitro and in vivo. Both purified flagellin and flagellated P. aeruginosa induced an MDSC phenotype distinct from that of the previously described MDSC-inducing cytokine GM-CSF, characterized by an upregulation of the chemokine receptor CXCR4 on the surface of MDSCs. Functionally, P. aeruginosa\u2013infected CF patient ex vivo\u2013isolated as well as flagellin or P. aeruginosa in vitro\u2013generated MDSCs efficiently suppressed polyclonal T cell proliferation in a dose-dependent manner and modulated Th17 responses. These studies demonstrate that flagellin induces the generation of MDSCs and suggest that P. aeruginosa uses this mechanism to undermine T cell\u2013mediated host defense in CF and other P. aeruginosa\u2013associated chronic lung diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1202144","type":"journal-article","created":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T02:47:15Z","timestamp":1357008435000},"page":"1276-1284","source":"Crossref","is-referenced-by-count":123,"title":["Flagellin Induces Myeloid-Derived Suppressor Cells: Implications for <i>Pseudomonas aeruginosa<\/i> Infection in Cystic Fibrosis Lung Disease"],"prefix":"10.1093","volume":"190","author":[{"given":"Nikolaus","family":"Rieber","sequence":"first","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hector","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Graepler-Mainka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ost","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Wecker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wirth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Mays","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Zundel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Handgretinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hogardt","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Frankfurt , Frankfurt, 60486","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"D\u00f6ring","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of T\u00fcbingen , T\u00fcbingen, 72076","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Riethm\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, University of T\u00fcbingen , T\u00fcbingen, 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