DC-SIGN and mannosylated surface structures of Mycobacterium tuberculosis: a deceptive liaison

Ehlers, Stefan

doi:10.1016/j.ejcb.2009.10.004

Cited by 61 publications

(49 citation statements)

References 59 publications

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“…The lprG mutant also has a cell envelope defect based on increased susceptibility to SDS which suggests the in vivo attenuation of the lprG mutant may be, in part, due to permeability to immune effectors such as antimicrobial peptides [20]. Other potential mechanisms of attenuation not investigated in this study include loss of LAM-dependent inhibition of protein kinase C activity [31], expansion of regulatory T cells [32], and suppression of a dendritic cell pro-inflammatory program [33]. Furthermore, although our results strongly indicate LAM orientation is the major factor that modulates the surface chemical property of the lprG mutant, we are unable to rule out the possibility that interaction of LprG with phosphatidylinositol mannosides, lipomannan, and/or other lipoglycan contributes to the phenotypes observed in the lprG mutant.…”

Section: Discussionmentioning

confidence: 99%

LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis

et al. 2014

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Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibition of phagosome-lysosome fusion, and intracellular survival, but in vivo evidence is lacking. LprG, a cell envelope lipoprotein that is essential for virulence of M. tuberculosis, has been shown to bind to the acyl groups of lipoglycans but the role of LprG in LAM biosynthesis and localization remains unknown. Using an M. tuberculosis lprG mutant, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. The lprG mutant had a normal quantity of LAM in the cell envelope, but its surface was altered and showed reduced expression of surface-exposed LAM. Functionally, the lprG mutant was defective for macrophage entry and inhibition of phagosome-lysosome fusion, was attenuated in macrophages, and was killed in the mouse lung with the onset of adaptive immunity. This study identifies the role of LprG in surface-exposed LAM expression and provides in vivo evidence for the essential role surface LAM plays in M. tuberculosis virulence. Findings have translational implications for therapy and vaccine development.

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Section: Discussionmentioning

confidence: 99%

LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis

et al. 2014

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“…tuberculosis and all other species of mycobacteria, many of which are opportunistic intracellular pathogens, owe much of their resilience to a distinctive lipid-rich cell envelope that not only protects the cells against harsh environments but also contains many molecules that are immune effectors crucial in evading the host immune response (Briken et al, 2004;Ishikawa et al, 2009;Schafer et al, 2009;Court et al, 2010;Ehlers, 2010;Philips and Ernst, 2012;Lang, 2013;Nobre et al, 2014). Besides glycolipids and glucans that constitute most of the M. tuberculosis cell envelope, several secreted proteins have been identified and shown to also play fundamental roles in M. tuberculosis survival and proliferation within the host (Abdallah et al, 2007;Philips, 2008;Philips and Ernst, 2012).…”

Section: Mycobacterium Tuberculosis: Biology and Infectionmentioning

confidence: 99%

Autophagy in the Fight Against Tuberculosis

Bento

Empadinhas

Mendes

2015

DNA and Cell Biology

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Tuberculosis (TB), a chronic infectious disease mainly caused by the tubercle bacillus Mycobacterium tuberculosis, is one of the world's deadliest diseases that has afflicted humanity since ancient times. Although the number of people falling ill with TB each year is declining, its incidence in many developing countries is still a major cause of concern. Upon invading host cells by phagocytosis, M. tuberculosis can replicate within infected cells by arresting the maturation of the phagosome whose function is to target the pathogen for elimination. Host cells have mechanisms of controlling this evasion by inducing autophagy, an elaborate cellular process that targets bacteria for progressive elimination, decreasing bacterial loads within infected cells. In addition, autophagy activation also aids in the control of inflammation, contributing to a more efficient innate immune response against M. tuberculosis. Several innovative TB therapies have been envisaged based on autophagy manipulation, with some of them revealing high potential for future clinical trials and eventual implementation in healthcare systems. Thus, this review highlights the recent advances on the innate immune response regulation by autophagy upon M. tuberculosis infection and the promising new autophagy-based therapies for TB. Mycobacterium tuberculosis: Biology and Infection

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“…The dendritic cell-specific C-type lectin, dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a calcium dependent carbohydrate-binding receptor with specificity, in part, for mannose-containing glycosides and Lewis antigens containing fucose [18] [19]. DC-SIGN, by virtue of interaction with highly mannosylated structures in the Mtb cell wall serves to impair DC maturation and induces the secretion of the anti-inflammatory cytokine IL-10 [20].…”

Section: Resultsmentioning

confidence: 99%

The presence of a galactosamine substituent on the arabinogalactan of Mycobacterium tuberculosis abrogates full maturation of human peripheral blood monocyte-derived dendritic cells and increases secretion of IL-10

et al. 2015

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SUMMARY Slow-growing and pathogenic Mycobacterium spp. are characterized by the presence of galactosamine (GalN) that modifies the interior branched arabinosyl residues of the arabinogalactan (AG) that is a major heteropolysaccharide cell wall component. The availability of null mutants of the polyprenyl-phospho-N-acetylgalactosaminyl synthase (Rv3631, PpgS) and the (N-acetyl-) galactosaminyl transferase (Rv3779) of Mycobacterium tuberculosis (Mtb) has provided a means to elucidate the role of the GalN substituent of AG in terms of host-pathogen interactions. Comparisons of treating human peripheral blood monocyte-derived dendritic cells (hPMC-DCs) with wild-type, Rv3631 and Rv3779 mutant strains of Mtb revealed increased expression of DC maturation markers, decreased affinity for a soluble DC-SIGN probe, reduced IL-10 secretion and increased TLR-2-mediated NF-κB activation among GalN-deficient Mtb strains compared to GalN-producing strains. Analysis of surface expression of a panel of defined or putative DC-SIGN ligands on both WT strains or either Rv3631 or Rv3779 mutant did not show significant differences suggesting that the role of the GalN substituent of AG may be to modulate access of the bacilli to immunologically-relevant receptor domains on DCs or contribute to higher ordered pathogen associated molecular pattern (PAMP)/pattern recognition receptor (PRR) interactions rather than the GalN-AG components having a direct immunological effect per se.

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DC-SIGN and mannosylated surface structures of Mycobacterium tuberculosis: a deceptive liaison

Cited by 61 publications

References 59 publications

LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis

LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis

Autophagy in the Fight Against Tuberculosis

The presence of a galactosamine substituent on the arabinogalactan of Mycobacterium tuberculosis abrogates full maturation of human peripheral blood monocyte-derived dendritic cells and increases secretion of IL-10

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