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Journal of Lipid Research, Vol. 46, 475-483, March 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Mycobacteria use their surface-exposed glycolipids to infect human macrophages through a receptor-dependent process

Christelle Villeneuve, Martine Gilleron, Isabelle Maridonneau-Parini, Mamadou Daffé, Catherine Astarie-Dequeker¹ and Gilles Etienne¹

Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et Biologie Structurale, Unité Mixte de Recherche 5089-Centre National de la Recherche Scientifique et Université Paul Sabatier, 31077 Toulouse, France

¹ To whom correspondence should be addressed. e-mail: catherine.astarie-dequeker{at}ipbs.fr (C.A-D.); gilles.etienne{at}ipbs.fr (G.E.)

Two subfamilies of the polar glycopeptidolipids (GPLs) located on the surface of Mycobacterium smegmatis, along with unknown phospholipids, were recently shown to participate in the nonopsonic phagocytosis of mycobacteria by human macrophages (Villeneuve, C., G. Etienne, V. Abadie, H. Montrozier, C. Bordier, F. Laval, M. Daffe, I. Maridonneau-Parini, and C. Astarie-Dequeker. 2003. Surface-exposed glycopeptidolipids of Mycobacterium smegmatis specifically inhibit the phagocytosis of mycobacteria by human macrophages. Identification of a novel family of glycopeptidolipids. J. Biol. Chem. 278: 51291–51300). As demonstrated herein, a phospholipid mixture that derived from the methanol-insoluble fraction inhibited the phagocytosis of M. smegmatis. Inhibition was essentially attributable to phosphatidylinositol mannosides (PIMs), namely PIM₂ and PIM₆, because the purified phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylinositol were inactive. This was further confirmed using purified PIM₂ and PIM₆ from M. bovis BCG that decreased by half the internalization of M. smegmatis. Both compounds 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) favored the particle entry through complement receptor 3. GPL III, but not PIM_2, also directed particle entry through the mannose receptor.

Therefore, surface-exposed mycobacterial PIM and polar GPL participate in the receptor-dependent internalization of mycobacteria in human macrophages.

Abbreviations: CR3, complement receptor 3; GPL, glycopeptidolipid; MALDI-TOF, matrix-assisted laser-desorption/ionization time of flight; Man-BSA, mannosylated bovine serum albumin; MDM, macrophages derived from monocytes; MR, mannose receptor; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PIM, phosphatidylinositol mannoside

Supplementary key words mycobacterium • phospholipids • phosphatidylinositol mannosides • phagocytosis

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