MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection.
dc.contributor.author | Verceles, Avelino C | |
dc.contributor.author | Bhat, Pavan | |
dc.contributor.author | Nagaria, Zain | |
dc.contributor.author | Martin, Destiny | |
dc.contributor.author | Patel, Harsh | |
dc.contributor.author | Ntem-Mensah, Afua | |
dc.contributor.author | Hyun, Sang W | |
dc.contributor.author | Hahn, Andrea | |
dc.contributor.author | Jeudy, Jean | |
dc.contributor.author | Cross, Alan S | |
dc.contributor.author | Lillehoj, Erik P | |
dc.contributor.author | Goldblum, Simeon E | |
dc.date.accessioned | 2021-11-30T17:51:44Z | |
dc.date.available | 2021-11-30T17:51:44Z | |
dc.date.issued | 2021-11-22 | |
dc.identifier.uri | http://hdl.handle.net/10713/17220 | |
dc.description.abstract | We 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.uri | https://doi.org/10.1038/s41598-021-02242-x | en_US |
dc.language.iso | en | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.ispartof | Scientific Reports | en_US |
dc.rights | © 2021. The Author(s). | en_US |
dc.subject | MUC1 ectodomain | en_US |
dc.subject.mesh | Biomarkers | en_US |
dc.subject.mesh | Flagellin | en_US |
dc.subject.mesh | Pneumonia, Ventilator-Associated | en_US |
dc.subject.mesh | Pseudomonas aeruginosa | en_US |
dc.subject.mesh | Pseudomonas Infections | en_US |
dc.title | MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection. | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1038/s41598-021-02242-x | |
dc.identifier.pmid | 34811449 | |
dc.source.journaltitle | Scientific reports | |
dc.source.volume | 11 | |
dc.source.issue | 1 | |
dc.source.beginpage | 22725 | |
dc.source.endpage | ||
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | England |