Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG

Carroll, Maria V.; Sim, Robert B.; Bigi, Fabiana; Jäkel, Anne; Antrobus, Robin; Mitchell, Daniel A.

doi:10.1007/s13238-010-0101-3

Cited by 45 publications

(33 citation statements)

References 58 publications

(69 reference statements)

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“…( C ) Listed are the human PRRs activated by Candida and Mycobacteria spp, alongside their cognate PAMPs from each pathogen class. The superscript number(s) next to each mycobacterial PAMP indicates a corresponding reference that documents its association with or activation of TLR2 245–247 , TLR4 248 , TLR6 249 , TLR9 250 , NOD2 251 , MINCLE 252 , MARCO 253 , Dectin-2 254 , Dectin-3 255 , Mannose Receptor 256,257 , CR 258,259 , DC-SIGN 260,261 , Galectin-3 262,263 , CD36 264 , MBL 265 , Dectin-1 266 , NLRP3 267 . The superscript number(s) next to each Candida PAMP indicates a corresponding reference that documents its activation of either TLR2 268–270 , TLR4 269,270 , Dectin-1 271 , Mannose Receptor 269 , Dectin-2 272,273 , DC-SIGN 274 , Galectin-3 275 , MINCLE 276 , SCARF1 277 , CD36 277 , MBL 278 , CR3 279 , Dectin-3 280 , TLR9 281,282 , NLRP3 283 , NOD2 282 .…”

Section: Figurementioning

confidence: 99%

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

Robinson

Huppler

2017

Cytokine

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Mycobacteria and Candida species include significant human pathogens that can cause localized or disseminated infections. Although these organisms may appear to have little in common, several shared pathways of immune recognition and response are important for both control and infection-related pathology. In this article, we compare and contrast the innate and adaptive components of the immune system that pertain to these infections in humans and animal models. We also explore a relatively new concept in the mycobacterial field: biological commensalism. Similar to the well-established model of Candida infection, Mycobacterial species colonize their human hosts in equilibrium with the immune response. Perturbations in the immune response permit the progression to pathologic disease at the expense of the host. Understanding the immune factors required to maintain commensalism may aid with the development of diagnostic and treatment strategies for both categories of pathogens.

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Section: Figurementioning

confidence: 99%

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

Robinson

Huppler

2017

Cytokine

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“…Infection studies with (human) DC-SIGN transgenic mice revealed that the lectin’s interaction with Mtb may likely serve as a strategy for host protection against Mtb -mediated tissue pathology and thus provide an environment of Mtb persistence as opposed to simply diminishing host immunity and favoring infection [19]. In addition to ManLAM, several other Mtb ligands such as the mannosylated 19 kDa (LpqH) lipoprotein, DnaK, the 45 kDa (alanine/proline-rich antigen, Apa) glycoproteins and hexamannosylated phosphatidyl- myo -inositol mannosides (PIM 6 ) have been proposed to bind DC-SIGN [5,22–24]. We thus sought to determine whether the GalN substituent on AG alters overall interaction of Mtb with DC-SIGN.…”

Section: Resultsmentioning

confidence: 99%

“…Bacteria were labeled with MoAb specific for LAM [20], 19 kDa protein [25], DnaK [24], and the 45–47 kDa antigen (Apa) [26]. Mouse MoAbs bound to Mtb were fluorescently labeled with a secondary Alexa fluor 488-conjugated anti-mouse IgG antibody and the geometric MFI was determined by flow cytometry (Figure 6).…”

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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“…SodA was detected as the major product of the 25-kDa langerin-reactive protein spots, and GroEL1 (presumably as degradation products of this protein) was detected in both the 28-and 25-kDa protein spots. SodA has been reported to specifically bind to surface of human respiratory epithelial cells (30), and M. bovis GroEL1 was shown to be DC-SIGN ligands (31). Although bioinformatics indicated that these two proteins are not glycosylated, their possible interaction with langerin in a carbohydrate-independent manner cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate-Dependent Binding of Langerin to SodC, a Cell Wall Glycoprotein of Mycobacterium leprae

Kim¹,

Brennan²,

Heaslip³

et al. 2014

J. Bacteriol.

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M ycobacterium leprae infections lead to human leprosy, characterized by disfiguring skin lesions, nerve damage, and eventually permanent disability (1). As part of the disease process, M. leprae is phagocytized by numerous cell types, including dendritic cells (DCs) and epidermal DCs known as Langerhans cells (LCs) (2-4). The cell envelopes of pathogenic Mycobacterium spp., including M. leprae, are rich in mannosylated macromolecules such as mannose-capped lipoarabinomannan (ManLAM), lipomannan (LM), phosphatidylinositol mannosides (PIM) and presumably glycoproteins (5, 6). These glycoconjugates contribute to the interaction of pathogenic mycobacteria with host phagocytes, and the C-type lectin receptors (CLRs) that decorate the surface of phagocytes have been shown to directly bind specific mannosylated glycoconjugates of Mycobacterium spp (7). For DCs, the constitutive CLRs are the mannose receptor (CD206) and the dendritic cell-specific intracellular adhesion moleculegrabbing nonintegrin (DC-SIGN; CD209). However, langerin (CD207) is a CLR specific to LCs. DC-SIGN and langerin recognize the sugar residues of macromolecules produced by pathogens and altered self-antigens in a calcium-dependent manner. These CLRs are comprised of a short cytoplasmic domain, a transmembrane domain, and, on the outer surface of the cell, an extracellular domain (ECD) that encompasses the highly conserved carbohydrate recognition domains (CRDs) and the hydrophobic neck domain. The CRDs determine sugar-binding specificity, and DC-SIGN and langerin possess an EPN (Glu-Pro-Asn) motif that is generally specific to oligosaccharides containing mannose (Man), fucose, glucose, or N-acetylglucosamine residues (8). The ␣-helix coiled-coil formation in the neck domains is responsible for the trimeric and tetrameric structures of langerin and DC-SIGN, respectively, and these multimeric conformations promote carbohydrate spatial specificity (9, 10). Some of mycobacterial ligands of DC-SIGN have been defined. Specifically, DC-SIGN recognizes the ␣(1¡2) linkages of ManLAM and PIM 6 (11,12). The 45-kDa and 19-kDa glycoproteins of Mycobacterium tuberculosis are also DC-SIGN ligands based on their inhibition of bacterial cell uptake via DC-SIGNtransfected cell lines (13). However, it should be noted that studies to directly compare the binding affinity of protein and lipoglycan ligands for C-type lectins or to define the relative contribution of each ligand have not been performed.We previously demonstrated that langerin-positive LCs present cell wall antigens of M. leprae to CD1a-restricted T cells, resulting in T cell proliferation and gamma interferon (IFN-␥) production (2). This study demonstrated the biological significance for the interaction of M. leprae ligands with the langerin of LCs; however, the M. leprae binding partners of this CLR were not elucidated. Thus, in the present work we sought to characterize the biochemical and biophysical features of the M. leprae glycoconjugates recognized by langerin.

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Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG

Cited by 45 publications

References 58 publications

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

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

Carbohydrate-Dependent Binding of Langerin to SodC, a Cell Wall Glycoprotein of Mycobacterium leprae

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