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A more recent version of this article appeared on March 1, 2005

Papers In Press, published online ahead of print December 1, 2004
J. Lipid Res., doi:10.1194/jlr.M400308-JLR200
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Submitted on August 13, 2004
Revised on November 4, 2004
Accepted on November 26, 2004

Surface-exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the receptor-dependent phagocytosis of mycobacteria by human macrophages

Christelle Villenuve, Martine Gilleron, Isabelle Maridonneau-Parini, Mamadou Daffe, Catherine Astarie-Dequeker, and Gilles Etienne

Mecanismes Moleculaires des Infections Mycobactériennes, IPBS du CNRS-UPS, Toulouse 31077

Corresponding Author: gilles.etienne{at}ipbs.fr

We have recently shown that two sub-families of the glycopeptidolipids (GPL) located on the surface of Mycobacterium smegmatis, along with unknown phospholipids, participate in the nonopsonic phagocytosis of mycobacteria by human macrophages (Villeneuve et al, 2003, J.Biol.Chem., 278, 51291-300). The latter compounds were purified and identified and their molecular mechanisms of action were examined in the present study. We showed that a phospholipid mixture that derived from the methanol-insoluble fraction inhibited the phagocytosis of M. smegmatis. This inhibition was attributable to phosphatidylinositol mannosides (PIM), namely PIM2 and PIM6, since the purified phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol were inactive. This observation was confirmed using purified PIM2 and PIM6 from M. bovis BCG that decreased by half the internalization of M. smegmatis. Both glycophospholipids also inhibited the uptake of M. tuberculosis and M. avium but had no effect on the internalization of zymosan used as a control particle of the phagocytic process. When coated on latex beads, PIM2 and polar GPL (GPL III) favoured the particle entry through complement receptor 3 (CR3). GPL III, but not PIM2, also directed particles entry through the mannose receptor (MR). Therefore, surface-exposed mycobacterial PIM and polar GPL participate to the receptor-dependent internalization of mycobacteria in human macrophages. As such, they constitute tools to dissect receptor-signalling pathway and, as inhibitors of phagocytosis, may help to design pharmacological drugs for the control of mycobacterial infections.


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