Host resistance to lung infection mediated by major vault protein in epithelial cells.
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.
Kowalski
Michael P
MP
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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
D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D015398:Signal Transduction; D020394:Vault Ribonucleoprotein Particles / Q000502:physiology*; D000099187:Major Vault Protein
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D034741:RNA, Small Interfering; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein