MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection.
AuthorVerceles, Avelino C
Hyun, Sang W
Cross, Alan S
Lillehoj, Erik P
Goldblum, Simeon E
MetadataShow full item record
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.
Rights/Terms© 2021. The Author(s).
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/17220
- Neuraminidase 1-mediated desialylation of the mucin 1 ectodomain releases a decoy receptor that protects against <i>Pseudomonas aeruginosa</i> lung infection.
- Authors: Lillehoj EP, Guang W, Hyun SW, Liu A, Hegerle N, Simon R, Cross AS, Ishida H, Luzina IG, Atamas SP, Goldblum SE
- Issue date: 2019 Jan 11
- NEU1 Sialidase Regulates Membrane-tethered Mucin (MUC1) Ectodomain Adhesiveness for Pseudomonas aeruginosa and Decoy Receptor Release.
- Authors: Lillehoj EP, Hyun SW, Liu A, Guang W, Verceles AC, Luzina IG, Atamas SP, Kim KC, Goldblum SE
- Issue date: 2015 Jul 24
- Pseudomonas aeruginosa stimulates tyrosine phosphorylation of and TLR5 association with the MUC1 cytoplasmic tail through EGFR activation.
- Authors: Kato K, Lillehoj EP, Kim KC
- Issue date: 2016 Mar
- The NEU1-selective sialidase inhibitor, C9-butyl-amide-DANA, blocks sialidase activity and NEU1-mediated bioactivities in human lung in vitro and murine lung in vivo.
- Authors: Hyun SW, Liu A, Liu Z, Cross AS, Verceles AC, Magesh S, Kommagalla Y, Kona C, Ando H, Luzina IG, Atamas SP, Piepenbrink KH, Sundberg EJ, Guang W, Ishida H, Lillehoj EP, Goldblum SE
- Issue date: 2016 Aug
- MUC1 expression by human airway epithelial cells mediates Pseudomonas aeruginosa adhesion.
- Authors: Kato K, Lillehoj EP, Kai H, Kim KC
- Issue date: 2010 Jan 1