Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity.
Interactions between dendritic cells and Mycobacterium tuberculosis, the aetiological agent of tuberculosis in humans, are thought to be central to anti-mycobacterial immunity. We have previously shown that M. tuberculosis binds to human monocyte-derived dendritic cells mostly through the C-type lectin DC-SIGN (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209, and we have suggested that DC-SIGN may discriminate between mycobacterial species through recognition of the mannose-capping residues on the lipoglycan lipoarabinomannan of the bacterial envelope. Here, using a variety of fast- and slow-growing Mycobacterium species, we provide further evidence that mycobacteria recognition by DC-SIGN may be restricted to species of the M. tuberculosis complex. Fine analyses of the lipoarabinomannan molecules purified from these species show that the structure and amount of these molecules alone cannot account for such a preferential recognition. We propose that M. tuberculosis recognition by DC-SIGN relies on both a potential difference of accessibility of lipoarabinomannan in its envelope and, more probably, on the binding of additional ligands, possibly including lipomannan, mannose-capped arabinomannan, as well as the mannosylated 19 kDa and 45 kDa [Apa (alanine/proline-rich antigen)] glycoproteins. Altogether, our results reveal that the molecular basis of M. tuberculosis binding to DC-SIGN is more complicated than previously thought and provides further insight into the mechanisms of M. tuberculosis recognition by the immune system.
Pitarque
Sylvain
S
Institut de Pharmacologie et de Biologie Structurale, Département Mécanismes Moléculaires des Infections Mycobactériennes, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex 4, France.
Herrmann
Jean-Louis
JL
Duteyrat
Jean-Luc
JL
Jackson
Mary
M
Stewart
Graham R
GR
Lecointe
François
F
Payre
Bruno
B
Schwartz
Olivier
O
Young
Douglas B
DB
Marchal
Gilles
G
Lagrange
Philippe H
PH
Puzo
Germain
G
Gicquel
Brigitte
B
Nigou
Jérôme
J
Neyrolles
Olivier
O
D001422:Bacterial Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013045:Species Specificity; D013379:Substrate Specificity; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin