title: CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung.
abstract: CD1d-restricted T cells are implicated as key players in host defense against various microbial infections. However, the mechanisms involved and the role they play, if any, at the mucosal surfaces where pathogenic infections are initiated is unknown. In a murine pneumonia model established by intranasal application of Pseudomonas aeruginosa, CD1d(-/-) mice showed markedly reduced pulmonary eradication of P. aeruginosa compared with wild-type mice; this was associated with significantly lower amounts of macrophage inflammatory protein-2 and reduced numbers of neutrophils within the bronchoalveolar lavage fluid. Corollarily, treatment of mice with alpha-galactosylceramide--a lipid that activates CD1d-restricted T cells--increased the amount of interferon-gamma; this was associated with rapid pulmonary clearance through enhanced phagocytosis of P. aeruginosa by alveolar macrophages. These results reveal a crucial role played by CD1d-restricted T cells in regulating the antimicrobial immune functions of macrophages at the lung mucosal surface.
authors.affiliation: Gastroenterology Division and Laboratory of Mucosal Immunology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Edward E S
authors.initials: EE
authors.lastname: Nieuwenhuis
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Mark
authors.initials: M
authors.lastname: Exley
authors.forename: Robbert A
authors.initials: RA
authors.lastname: Schleipman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Glickman
authors.forename: Dan T
authors.initials: DT
authors.lastname: Bailey
authors.forename: Nadia
authors.initials: N
authors.lastname: Corazza
authors.forename: Sean P
authors.initials: SP
authors.lastname: Colgan
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Onderdonk
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2