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

作者：Tanne Antoine; Ma Bo; Boudou Frederic; Tailleux Ludovic; Botella Helene; Badell Edgar; Levillain Florence; Taylor Maureen E; Drickamer Kurt; Nigou Jerome; Dobos Karen M; Puzo Germain; Vestweber Dietmar; Wild Martin K; Marcinko Marie; Sobieszczuk Peter; Stewart Lauren; Lebus Daniel; Gicquel Brigitte; Neyrolles Olivier^*

来源：Journal of Experimental Medicine, 2009, 206(10): 2205-2220.

DOI：10.1084/jem.20090188

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. tuber-culosis 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.

• 出版日期2009-9-28