Comparative effects of <i>Mycobacterium avium</i> glycopeptidolipid and lipopeptide fragment on the function and ultrastructure of mononuclear cells

Pourshafie, Mohammad Reza; Ayub, Q.; Barrow, William W.

doi:10.1111/j.1365-2249.1993.tb06499.x

Cited by 25 publications

(11 citation statements)

References 41 publications

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“…(2000) demonstrating that human peripheral blood mononuclear cells (PBMC) pre‐treated with GPLs from serovars 4 and 8 showed a diminished production of IL‐12 and IFN‐γ following phorbol 12‐myristate 13‐acetate (PMA) treatment. These results and others (Pourshafie et al ., 1993; Barrow et al ., 1995) suggest that GPLs have immune modulatory activity and can affect macrophage activation. However, these studies used crude lipid fractions or purified GPLs and it is unclear whether GPLs within the mycobacteria cell wall maintain similar immune suppression activity.…”

Section: Discussionsupporting

confidence: 89%

Elevated mitogen-activated protein kinase signalling and increased macrophage activation in cells infected with a glycopeptidolipid-deficient Mycobacterium avium

Bhatnagar

Schorey

2006

Cell Microbiol

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SummaryMycobacterium avium is a significant cause of morbidity and mortality in AIDS patients. M. avium can be isolated as three major morphotypes: smooth-transparent ( SmT ), smooth-opaque ( SmO ) and rough ( Rg ). Studies indicate that many Rg isolates lack or have modified glycopeptidolipids (GPLs). GPLs are major surface constituents of the M. avium cell wall and heterogeneity in their carbohydrate moieties has been used to classify M. avium into different serotypes, with serotypes 1, 4 and 8 being isolated with high frequency from AIDS patients. However, it is unclear what role GPLs play in M. avium pathogenicity. To begin to address how the absence of GPLs affects M. avium -macrophage interaction, we used the wellcharacterized M. avium 2151 SmT and Rg isolates which differ in GPL expression. We found macrophages infected with the Rg compared with SmT M. avium 2151 showed prolonged activation of the mitogen-activated protein kinases (MAPKs) p38 and ERK1/2. Macrophages infected with the Rg 2151 also showed increased tumour necrosis factor-α α α α (TNF-α α α α ) production. Interestingly, TNF-α α α α secretion by macrophages infected with SmO or SmT 2151 was dependent on p38, ERK1/2 and NF-κ κ κ κ B while TNF-α α α α secretion by Rg 2151-infected macrophages was dependent on NF-κ κ κ κ B but not the MAPKs. Rg 2151-infected macrophages also produced increased levels of IL-6, IL-12, MCP-1 and RANTES relative to macrophages infected with SmT 2151. These results indicate that M. avium 2151 deficient in GPLs promote increased macrophage activation. This disparity in cellular activation stems from a quantitative and qualitative difference in the macrophage signalling response to the Rg and SmT M. avium 2151.

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Section: Discussionsupporting

confidence: 89%

Elevated mitogen-activated protein kinase signalling and increased macrophage activation in cells infected with a glycopeptidolipid-deficient Mycobacterium avium

Bhatnagar

Schorey

2006

Cell Microbiol

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“…During infection, M. avium synthesizes GPLs that accumulate in macrophages [278,[282][283][284]. Early studies have shown that M. avium ssGPLs suppress the mitogen-induced proliferative responses of murine splenic cells [285][286][287] but not that of human peripheral blood mononuclear cells (PBM) [288]. More recently, GPLs from M. avium serovar 4 have been proposed to participate in the ability of M. avium to invade human macrophages and escape bactericidal responses [289].…”

Section: Biological Properties Of Gplsmentioning

confidence: 99%

Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

Daffé

Crick

Jackson

2015

Molecular Genetics of Mycobacteria

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This chapter summarizes what is currently known of the structures, physiological roles, involvement in pathogenicity and biogenesis of a variety of non-covalently bound cell envelope lipids and glycoconjugates of Mycobacterium tuberculosis and other Mycobacterium species. Topics addressed in this chapter include phospholipids; phosphatidylinositol mannosides; triglycerides; isoprenoids and related compounds (polyprenyl phosphate, menaquinones, carotenoids, non-carotenoid cyclic isoprenoids); acyltrehaloses (lipooligosaccharides, trehalose mono-and di-mycolates, sulfolipids, di-and poly-acyltrehaloses); mannosyl-beta-1phosphomycoketides; glycopeptidolipids; phthiocerol dimycocerosates, para-hydroxybenzoic acids and phenolic glycolipids; mycobactins; mycolactones; and capsular polysaccharides.

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“…Therefore, we and others have begun to dissect the interactions between GPLs and macrophages, as well as other host cells (18,20,23). We have observed that the proinflammatory response induced by GPLs is MyD88-and Toll-like receptor 2 (TLR2) dependent, suggesting that certain GPLs have the necessary structure to signal through this receptor (23).…”

Section: Discussionmentioning

confidence: 99%

Mannose Receptor-Dependent Delay in Phagosome Maturation by Mycobacterium avium Glycopeptidolipids

et al. 2010

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The ability of pathogenic mycobacteria to block phagosome-lysosome fusion is critical for its pathogenesis. The molecules expressed by mycobacteria that inhibit phagosome maturation and the mechanism of this inhibition have been extensively studied. Recent work has indicated that mannosylated lipoarabinomannan (ManLAM) isolated from Mycobacterium tuberculosis can function to delay phagosome-lysosome fusion and that this delay requires the interaction of ManLAM with the mannose receptor (MR). However, the molecules expressed by other pathogenic mycobacteria that function to inhibit phagosome maturation have not been well described. In the present study, we show that phagosomes containing silica beads coated with glycopeptidolipids (GPLs), a major surface component of Mycobacterium avium, showed limited acidification and delayed recruitment of late endosomal/lysosomal markers compared to those of phosphatidylcholine-coated beads. The carbohydrate component of the GPLs was required, as beads coated only with the lipopeptide core failed to delay phagosome-lysosome fusion. Moreover, the ability of GPLs to delay phagosome maturation was dependent on the macrophage expression of the MR. Using CHO cells expressing the MR, we confirmed that the GPLs bind this receptor. Finally, human monocyte-derived macrophages knocked down for MR expression showed increased M. avium phagosome-lysosome fusion relative to control cells. Together, the data indicate that GPLs can function to delay phagosome-lysosome fusion and suggest that GPLs, like ManLAM, work through the MR to mediate this activity.Mycobacterium avium, a prominent opportunistic pathogen in AIDS patients and a source of pulmonary infections in non-AIDS patients, is an intracellular pathogen which resides primarily in host macrophages. Like most pathogenic mycobacteria, M. avium resides within a phagosome which fails to mature to a phagolysosome (22). Phagosomes containing viable M. avium retain early endosomal markers such as Rab5 and the transferrin receptor but lack complete luminal acidification and recruitment of late endosomal/lysosomal markers (7,14,27,28). The mechanism by which pathogenic mycobacteria are able to block phagosome-lysosome (P-L) fusion is of great interest, and how Mycobacterium tuberculosis performs this function has been extensively studied (27). Studies from Deretic and colleagues support that live M. tuberculosis blocks the normal calcium rise initiated upon a phagocytic response, the result of which leads to a diminished recruitment of type III phosphatidyl-inositol-3-kinase VPS34 to the phagosome, which limits phosphatidyl-inositol-3-phosphate (PI3P) formation and association of PI3P binding proteins such as early endosomal antigen 1 (EEA1) (8,26). The result is a loss in the tethering and fusion of late endosomes with the mycobacterial phagosome (8, 26).The M. tuberculosis surface-located mannosylated lipoarabinomannan (ManLAM) has been implicated in delaying P-L fusion. Published reports indicate that ManLAM can block the calcium influx re...

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Comparative effects of Mycobacterium avium glycopeptidolipid and lipopeptide fragment on the function and ultrastructure of mononuclear cells

Cited by 25 publications

References 41 publications

Elevated mitogen-activated protein kinase signalling and increased macrophage activation in cells infected with a glycopeptidolipid-deficient Mycobacterium avium

Elevated mitogen-activated protein kinase signalling and increased macrophage activation in cells infected with a glycopeptidolipid-deficient Mycobacterium avium

Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

Mannose Receptor-Dependent Delay in Phagosome Maturation by Mycobacterium avium Glycopeptidolipids

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