title: A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis.
abstract: The C-type lectin dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) mediates the innate immune recognition of microbial carbohydrates. We investigated the function of this molecule in the host response to pathogens in vivo, by generating mouse lines lacking the DC-SIGN homologues SIGNR1, SIGNR3, and SIGNR5. Resistance to Mycobacterium tuberculosis was impaired only in SIGNR3-deficient animals. SIGNR3 was expressed in lung phagocytes during infection, and interacted with M. tuberculosis bacilli and mycobacterial surface glycoconjugates to induce secretion of critical host defense inflammatory cytokines, including tumor necrosis factor (TNF). SIGNR3 signaling was dependent on an intracellular tyrosine-based motif and the tyrosine kinase Syk. Thus, the mouse DC-SIGN homologue SIGNR3 makes a unique contribution to protection of the host against a pulmonary bacterial pathogen.
authors.affiliation: Centre National de la Recherche Scientifique, Université de Toulouse, Toulouse, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Tanne
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boudou
authors.forename: Ludovic
authors.initials: L
authors.lastname: Tailleux
authors.forename: Hélène
authors.initials: H
authors.lastname: Botella
authors.forename: Edgar
authors.initials: E
authors.lastname: Badell
authors.forename: Florence
authors.initials: F
authors.lastname: Levillain
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Taylor
authors.forename: Kurt
authors.initials: K
authors.lastname: Drickamer
authors.forename: Jérome
authors.initials: J
authors.lastname: Nigou
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dobos
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Martin K
authors.initials: MK
authors.lastname: Wild
authors.forename: Marie
authors.initials: M
authors.lastname: Marcinko
authors.forename: Peter
authors.initials: P
authors.lastname: Sobieszczuk
authors.forename: Lauren
authors.initials: L
authors.lastname: Stewart
authors.forename: Daniel
authors.initials: D
authors.lastname: Lebus
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Olivier
authors.initials: O
authors.lastname: Neyrolles
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D006001:Glycoconjugates / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D048049:Extracellular Signal-Regulated MAP Kinases; D006001:Glycoconjugates; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019908:Proto-Oncogene Proteins c-raf; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C494354:SIGNR3 protein, mouse; C493486:Tlr2 protein, mouse; C050016:lipoarabinomannan