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Host resistance to lung infection mediated by major vault protein in epithelial cells.

ABSTRACT: The airway epithelium plays an essential role in innate immunity to lung pathogens. Ribonucleoprotein particles primarily composed of major vault protein (MVP) are highly expressed in cells that encounter xenobiotics. However, a clear biologic function for MVP is not established. We report here that MVP is rapidly recruited to lipid rafts when human lung epithelial cells are infected with Pseudomonas aeruginosa, and maximal recruitment is dependent on bacterial binding to the cystic fibrosis transmembrane conductance regulator. MVP was also essential for optimal epithelial cell internalization and clearance of P. aeruginosa. These results suggest that MVP makes a substantial contribution to epithelial cell-mediated resistance to infection.

SUBMITTER: Kowalski MP

PROVIDER: S-EPMC3685177 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Host resistance to lung infection mediated by major vault protein in epithelial cells.

Kowalski Michael P MP Dubouix-Bourandy Anne A Bajmoczi Milan M Golan David E DE Zaidi Tanweer T Coutinho-Sledge Yamara S YS Gygi Melanie P MP Gygi Steven P SP Wiemer Erik A C EA Pier Gerald B GB

Science (New York, N.Y.) 20070701 5834

The airway epithelium plays an essential role in innate immunity to lung pathogens. Ribonucleoprotein particles primarily composed of major vault protein (MVP) are highly expressed in cells that encounter xenobiotics. However, a clear biologic function for MVP is not established. We report here that MVP is rapidly recruited to lipid rafts when human lung epithelial cells are infected with Pseudomonas aeruginosa, and maximal recruitment is dependent on bacterial binding to the cystic fibrosis tra ...[more]

PMID: 17615361

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IL-25 promotes cisplatin resistance of lung cancer cells by activating NF-κB signaling pathway to increase of major vault protein.

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Selection and characterisation of a phage-displayed human antibody (Fab) reactive to the lung resistance-related major vault protein.

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Expression of the Major Vault Protein (MVP) and Cellular Vault Particles in Fish.

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Project description:Streptococcus pneumoniae (Spn) alone and during co-infection with influenza A virus (IAV) can result in severe pneumonia with mortality. Pneumococcal surface protein A (PspA) is an established virulence factor required for Spn evasion of lactoferricin and C-reactive protein-activated complement-mediated killing. Herein, we show that PspA functions as an adhesin to dying host cells. We demonstrate that PspA binds to host-derived glyceraldehyde-3-phosphate dehydrogenase (GAPDH) bound to outward-flipped phosphatidylserine residues on dying host cells. PspA-mediated adhesion was to apoptotic, pyroptotic, and necroptotic cells, but not healthy lung cells. Using isogenic mutants of Spn, we show that PspA-GAPDH-mediated binding to lung cells increases pneumococcal localization in the lower airway, and this is enhanced as a result of pneumolysin exposure or co-infection with IAV. PspA-mediated binding to GAPDH requires amino acids 230-281 in its α-helical domain with intratracheal inoculation of this PspA fragment alongside the bacteria reducing disease severity in an IAV/Spn pneumonia model.

| S-EPMC8265312 | biostudies-literature

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