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dc.contributor.authorVerceles, Avelino C
dc.contributor.authorBhat, Pavan
dc.contributor.authorNagaria, Zain
dc.contributor.authorMartin, Destiny
dc.contributor.authorPatel, Harsh
dc.contributor.authorNtem-Mensah, Afua
dc.contributor.authorHyun, Sang W
dc.contributor.authorHahn, Andrea
dc.contributor.authorJeudy, Jean
dc.contributor.authorCross, Alan S
dc.contributor.authorLillehoj, Erik P
dc.contributor.authorGoldblum, Simeon E
dc.date.accessioned2021-11-30T17:51:44Z
dc.date.available2021-11-30T17:51:44Z
dc.date.issued2021-11-22
dc.identifier.urihttp://hdl.handle.net/10713/17220
dc.description.abstractWe previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.en_US
dc.description.urihttps://doi.org/10.1038/s41598-021-02242-xen_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofScientific Reportsen_US
dc.rights© 2021. The Author(s).en_US
dc.subjectMUC1 ectodomainen_US
dc.subject.meshBiomarkersen_US
dc.subject.meshFlagellinen_US
dc.subject.meshPneumonia, Ventilator-Associateden_US
dc.subject.meshPseudomonas aeruginosaen_US
dc.subject.meshPseudomonas Infectionsen_US
dc.titleMUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection.en_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-021-02242-x
dc.identifier.pmid34811449
dc.source.journaltitleScientific reports
dc.source.volume11
dc.source.issue1
dc.source.beginpage22725
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland


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