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PMID:19770268

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Citation

Tanne, A, Ma, B, Boudou, F, Tailleux, L, Botella, H, Badell, E, Levillain, F, Taylor, ME, Drickamer, K, Nigou, J, Dobos, KM, Puzo, G, Vestweber, D, Wild, MK, Marcinko, M, Sobieszczuk, P, Stewart, L, Lebus, D, Gicquel, B and Neyrolles, O (2009) A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis. J. Exp. Med. 206:2205-20

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.

Links

PubMed PMC2757888 Online version:10.1084/jem.20090188

Keywords

Animals; Antigens, CD/physiology; Cell Adhesion Molecules/physiology; Extracellular Signal-Regulated MAP Kinases/physiology; Female; Glycoconjugates/metabolism; Interleukin-6/biosynthesis; Lectins, C-Type/physiology; Lipopolysaccharides/metabolism; Lung/immunology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B/physiology; Proto-Oncogene Proteins c-raf/physiology; Receptors, Cell Surface/physiology; Signal Transduction; Toll-Like Receptor 2/physiology; Tuberculosis/immunology; Tumor Necrosis Factor-alpha/biosynthesis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KSYK

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2157947

P

Seeded From UniProt

complete

MOUSE:C209B

enables

GO:0005537: mannose binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:C209B

involved_in

GO:0006897: endocytosis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:C209D

enables

GO:0005537: mannose binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:C209D

involved_in

GO:0006897: endocytosis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:C209D

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:C209D

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1346060

P

Seeded From UniProt

complete

MOUSE:C209D

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:99515

P

Seeded From UniProt

complete

MOUSE:C209D

involved_in

GO:0042742: defense response to bacterium

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5052162

P

Seeded From UniProt

complete

MOUSE:TLR2

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2157947

P

Seeded From UniProt

complete

MOUSE:KSYK

acts_upstream_of_or_within

GO:0050715: positive regulation of cytokine secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2157947

P

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0050715: positive regulation of cytokine secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2157947

P

Seeded From UniProt

complete


See also

References

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