A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis

Antoine Tanne, Bo Ma, Frédéric Boudou, Ludovic Tailleux, Hélène Botella, Edgar Badell, Florence Levillain, Maureen E Taylor, Kurt Drickamer, Jérome Nigou, Karen M Dobos, Germain Puzo, Dietmar Vestweber, Martin K Wild, Marie Marcinko, Peter Sobieszczuk, Lauren Stewart, Daniel Lebus, Brigitte Gicquel, Olivier Neyrolles

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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.

OriginalsprogEngelsk
TidsskriftJournal of Experimental Medicine
Vol/bind206
Nummer10
Sider (fra-til)2205-20
Antal sider16
ISSN0022-1007
DOI
StatusUdgivet - 28 sep. 2009

Emneord

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

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