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

Antoine Tanne (1, 2) , Bo Ma (3) , Ludovic Tailleux (1) , Frédéric Boudou (1) , Hélène Botella (2) , Edgar Badell (1) , Florence Levillain (2) , Maureen Taylor (4) , Kurt Drickamer (4) , Jérome Nigou (2) , Karen Dobos (5) , Germain Puzo (2) , Dietmar Vestweber (6) , Martin Wild (6) , Marie Marcinko (3) , Peter Sobieszczuk (3) , Lauren Stewart (3) , Daniel Lebus (3) , Brigitte Gicquel (1) , Olivier Neyrolles (2, 1)

1 Génétique mycobactérienne - Mycobacterial genetics
2 IPBS - Institut de pharmacologie et de biologie structurale
3 The Scripps Research Institute [La Jolla, San Diego]
4 Imperial College London
5 CSU - Colorado State University [Fort Collins]
6 Max Planck Institute for Molecular Biomedicine

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.

Domaines: Maladies infectieuses; Immunité innée; Bactériologie

Antoine Tanne, Bo Ma, Ludovic Tailleux, Frédéric Boudou, Hélène Botella, et al.. A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis. Journal of Experimental Medicine, 2009, 206 (10), pp.2205-2220. ⟨10.1084/jem.20090188⟩. ⟨pasteur-03525480⟩