title: Mast cells protect against Pseudomonas aeruginosa-induced lung injury.
abstract: Pseudomonas aeruginosa, an opportunistic pathogen, is the leading cause of morbidity and mortality in immune-compromised individuals. Maintaining the integrity of the respiratory epithelium is critical for an effective host response to P. aeruginosa. Given the close spatial relationship between mast cells and the respiratory epithelium, and the importance of tightly regulated epithelial permeability during lung infections, we examined whether mast cells influence airway epithelial integrity during P. aeruginosa lung infection in a mouse model. We found that mast cell-deficient Kit(W-sh)/Kit(W-sh) mice displayed greatly increased epithelial permeability, bacterial dissemination, and neutrophil accumulation compared with wild-type animals after P. aeruginosa infection; these defects were corrected on reconstitution with mast cells. An in vitro Transwell co-culture model further demonstrated that a secreted mast cell factor decreased epithelial cell apoptosis and tumor necrosis factor production after P. aeruginosa infection. Together, our data demonstrate a previously unrecognized role for mast cells in the maintenance of epithelial integrity during P. aeruginosa infection, through a mechanism that likely involves prevention of epithelial apoptosis and tumor necrosis factor production. Our understanding of mechanisms of the host response to P. aeruginosa will open new avenues for the development of successful preventative and treatment strategies.
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Junkins
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Svetlana O
authors.initials: SO
authors.lastname: Carrigan
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stadnyk
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cowley
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Issekutz
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Berman
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: tong-jun.lin@dal.ca.
authors.forename: Tong-Jun
authors.initials: TJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D055370:Lung Injury / Q000276:immunology / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D011552:Pseudomonas Infections / Q000276:immunology / Q000473:pathology*; D011550:Pseudomonas aeruginosa; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000473:pathology*