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

 

Antoine Tanne1,2,3, Bo Ma4, Frédéric Boudou3, Ludovic Tailleux3, Hélène Botella1,2, Edgar Badell3, Florence Levillain1,2, Maureen E. Taylor5, Kurt Drickamer5, Jérome Nigou1,2, Karen M. Dobos6, Germain Puzo1,2, Dietmar Vestweber7, Martin K. Wild7, Marie Marcinko4, Peter Sobieszczuk4, Lauren Stewart4, Daniel Lebus4, Brigitte Gicquel3, and Olivier Neyrolles1,2,3

 

1 Centre National de la Recherche Scientifique, 2 Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse, France
3 Mycobacterial Genetics Unit, Institut Pasteur, 75724 Paris, France
4 Consortium for Functional Glycomics, Department of Chemical Physiology, the Scripps Research Institute, La Jolla, CA 92037
5 Division of Molecular Biosciences, Imperial College, London SW7 2AZ, England, UK
6 Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523
7 Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany

 

CORRESPONDENCE Olivier Neyrolles: olivier.neyrolles@ipbs.fr

 

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.