MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection

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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Avelino C. Verceles, Pavan Bhat, Zain Nagaria, Destiny Martin, Harsh Patel, Afua Ntem-Mensah, Sang W. Hyun, Andrea Hahn, Jean Jeudy, Alan S. Cross, Erik P. Lillehoj, Simeon E. Goldblum
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/4e92ed863fcf4e86a43cdd61abc11314
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:4e92ed863fcf4e86a43cdd61abc11314
record_format dspace
spelling oai:doaj.org-article:4e92ed863fcf4e86a43cdd61abc113142021-11-28T12:21:53ZMUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection10.1038/s41598-021-02242-x2045-2322https://doaj.org/article/4e92ed863fcf4e86a43cdd61abc113142021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02242-xhttps://doaj.org/toc/2045-2322Abstract 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.Avelino C. VercelesPavan BhatZain NagariaDestiny MartinHarsh PatelAfua Ntem-MensahSang W. HyunAndrea HahnJean JeudyAlan S. CrossErik P. LillehojSimeon E. GoldblumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Avelino C. Verceles
Pavan Bhat
Zain Nagaria
Destiny Martin
Harsh Patel
Afua Ntem-Mensah
Sang W. Hyun
Andrea Hahn
Jean Jeudy
Alan S. Cross
Erik P. Lillehoj
Simeon E. Goldblum
MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection
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.
format article
author Avelino C. Verceles
Pavan Bhat
Zain Nagaria
Destiny Martin
Harsh Patel
Afua Ntem-Mensah
Sang W. Hyun
Andrea Hahn
Jean Jeudy
Alan S. Cross
Erik P. Lillehoj
Simeon E. Goldblum
author_facet Avelino C. Verceles
Pavan Bhat
Zain Nagaria
Destiny Martin
Harsh Patel
Afua Ntem-Mensah
Sang W. Hyun
Andrea Hahn
Jean Jeudy
Alan S. Cross
Erik P. Lillehoj
Simeon E. Goldblum
author_sort Avelino C. Verceles
title MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection
title_short MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection
title_full MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection
title_fullStr MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection
title_full_unstemmed MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection
title_sort muc1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during pseudomonas aeruginosa lung infection
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/4e92ed863fcf4e86a43cdd61abc11314
work_keys_str_mv AT avelinocverceles muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT pavanbhat muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT zainnagaria muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT destinymartin muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT harshpatel muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT afuantemmensah muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT sangwhyun muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT andreahahn muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT jeanjeudy muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT alanscross muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT erikplillehoj muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
AT simeonegoldblum muc1ectodomainisaflagellintargetingdecoyreceptorandbiomarkeroperativeduringpseudomonasaeruginosalunginfection
_version_ 1718408011405328384