A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis.
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.
Tanne
Antoine
A
Centre National de la Recherche Scientifique, Université de Toulouse, Toulouse, France.
Ma
Bo
B
Boudou
Frédéric
F
Tailleux
Ludovic
L
Botella
Hélène
H
Badell
Edgar
E
Levillain
Florence
F
Taylor
Maureen E
ME
Drickamer
Kurt
K
Nigou
Jérome
J
Dobos
Karen M
KM
Puzo
Germain
G
Vestweber
Dietmar
D
Wild
Martin K
MK
Marcinko
Marie
M
Sobieszczuk
Peter
P
Stewart
Lauren
L
Lebus
Daniel
D
Gicquel
Brigitte
B
Neyrolles
Olivier
O
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
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