{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:47:36Z","timestamp":1771922856083,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      is a prevalent pathogen in persons with cystic fibrosis (pwCF), frequently causing chronic infections. These infections are often associated with episodic pulmonary exacerbations (PEx), yet the mechanisms linking changes in\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      to these PEx remain poorly understood. It is unknown whether virulence changes in\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      extracellular vesicles (EVs) contribute to PEx. We hypothesized that\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      EVs from PEx will elicit increased inflammation response compared to Pa EVs from clinical stability in an\n                      <jats:italic>in vitro<\/jats:italic>\n                      cell culture model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      EVs were isolated from the sputum of pwCF collected at PEx and the immediately preceding clinical stability period.\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      EVs or MEM control were applied apically to primary human bronchial epithelial (HBE) cells at air-liquid interface in the presence or absence of elexacaftor\/tezacaftor\/ivacaftor (ETI). Basal media and apical cell secretions were measured for 10 inflammatory cytokines using MesoScale Discovery (MSD) assays. RNAseq was performed on the HBE cells, with differential canonical pathways identified using Ingenuity Pathway Analysis (IPA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      EVs at PEx induced reduced cytokine production in both HBE donors in the presence of ETI (p&amp;lt;0.001 except apical TNF-\u03b1 p=0.022). The IPA results, which were hypothesis generating, suggested that the S-100 family pathway may be another measure of inflammation that is useful to study in CF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      EVs induced HBE cell inflammation, which was reduced in the presence of ETI.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1745853","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:14:45Z","timestamp":1769058885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of host inflammatory pathways by Pseudomonas aeruginosa extracellular vesicles in cystic fibrosis: impact of pulmonary exacerbation and elexacaftor-tezacaftor-ivacaftor treatment"],"prefix":"10.3389","volume":"17","author":[{"given":"Marianna","family":"Said","sequence":"first","affiliation":[{"name":"Center for Precision Medicine and Genomics Research, Children\u2019s National Research Institute","place":["Washington, DC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aszia","family":"Burrell","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine and Genomics Research, Children\u2019s National Research Institute","place":["Washington, DC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brennan","family":"Harmon","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine and Genomics Research, Children\u2019s National Research Institute","place":["Washington, DC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylie 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