Mycobacteria use their surface-exposed glycolipids to infect human macrophages through a receptor-dependent process.
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 PIM2, 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.
Villeneuve
Christelle
C
Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et Biologie Structurale, Unité Mixte de Recherche 5089-Centre National de la Recherche Scientifique, Université Paul Sabatier, 31077 Toulouse, France.
Gilleron
Martine
M
Maridonneau-Parini
Isabelle
I
Daffé
Mamadou
M
Astarie-Dequeker
Catherine
C
Etienne
Gilles
G
D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D006017:Glycolipids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009163:Mycobacterium bovis / Q000737:chemistry; D020102:Mycobacterium smegmatis / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000737:chemistry / Q000494:pharmacology
D006017:Glycolipids; D016177:Macrophage-1 Antigen; D010716:Phosphatidylinositols; C034154:phosphatidylinositol mannoside