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-Dequeker,Gilles Etienne

doi:10.1194/jlr.m400308-jlr200

Christelle Villeneuve, Martine Gilleron + Show 4 more

Open Access

https://doi.org/10.1194/jlr.m400308-jlr200

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Abstract

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.

Highlights

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
Using a biological test of phagocytosis inhibition, we found that lipids, but not proteins, isolated from the outermost layer of Mycobacterium smegmatis by a mechanical treatment decrease the nonopsonic phagocytosis of mycobacteria by human macrophages without affecting the internalization of particles such as zymosan or latex beads [20]
macrophages derived from monocytes (MDM) were pretreated for 15 min with the phospholipid-enriched extract at concentrations ranging from 10 pg to 100 ␮g lipid/ml and put into contact with M. smegmatis for 45 min

Summary

Introduction

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 Surface-exposed glycopeptidolipids of Mycobacterium smegmatis inhibit the phagocytosis of mycobacteria by human macrophages. Sonized particles [15, 16] Another one, located on the carboxyl-terminal end of the extracellular portion of CD11b, is a nonopsonic binding site with lectin properties [17]. This latter domain is mainly involved in phagocytosis of particles containing ␤-glucan, such as zymosan [18], and interacts with mannose, glucose, and N-acetyl-d-glucosamine [17]. A second nonopsonic binding domain distinct from the lectin one has been proposed to bind and internalize mycobacteria [19]

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