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Taxonomic group: protista / Euglenozoa (Phylum: Euglenozoa)
Host organism: Homo sapiens
Organ / tissue: Life stage: procyclic promastigote
Associated disease: infection due to Leishmania [ICD11: XN8JE

]; visceral leishmaniasis [ICD11: 1F54.0

, ICD11: XN8JE

]

NCBI PubMed ID: 23497381
Publication DOI: 10.1186/1756-3305-6-54
Journal NLM ID: 101462774
Publisher: London: BioMed Central
Correspondence: rsoares

cpqrr.fiocruz.br
Institutions: Centro de Pesquisas Rene Rachou, Fundacao Oswaldo Cruz - FIOCRUZ, Av, Augusto de Lima, 1715, Belo Horizonte, 30190-002, Brazil

Background: The dominant, cell surface lipophosphoglycan (LPG) of Leishmania is a multifunctional molecule involved in the interaction with vertebrate and invertebrate hosts. Although the role of LPG on infection has been extensively studied, it is not known if LPG interspecies variations contribute to the different immunopathologies of leishmaniases. To investigate the issue of interspecies polymorphisms, two Leishmania species from the New World that express structural variations of side chains of LPG repeat units were examined. In this context, the procyclic form of L. braziliensis LPG (strain M2903), is devoid of side chains, while the L. infantum LPG (strain BH46) has up to three glucoses residues in the repeat units. Methods: Mice peritoneal macrophages from Balb/c, C57BL/6 and knock-out (TLR2 -/-, TLR4 -/-) were primed with IFN-γ and stimulated with purified LPG from both species. Nitric oxide and cytokine production, MAPKs (ERK, p38 and JNK) and NF-kB activation were evaluated. Results: Macrophages stimulated with L. braziliensis LPG, had a higher TNF-α, IL-1β, IL-6 and NO production than those stimulated with that of L. infantum. Furthermore, the LPGs from the two species resulted in differential kinetics of signaling via MAPK activation. L. infantum LPG exhibited a gradual activation profile, whereas L. braziliensis LPG showed a sharp but transient activation. L. braziliensis LPG was able to activate NF-kB. Conclusion: These data suggest that two biochemically distinct LPGs were able to differentially modulate macrophage functions.

Leishmania braziliensis, Leishmania infantum, Lipophosphoglycan (LPG), Macrophage modulation, procyclic form

Structure type: oligomer
Location inside paper: Fig. 1, LPG - type III
Compound class: LPG
Contained glycoepitopes: IEDB_130701,IEDB_134623,IEDB_134624,IEDB_135614,IEDB_136044,IEDB_136095,IEDB_136100,IEDB_136906,IEDB_137472,IEDB_140628,IEDB_141794,IEDB_141806,IEDB_141807,IEDB_142349,IEDB_142350,IEDB_142488,IEDB_144983,IEDB_144993,IEDB_144996,IEDB_144998,IEDB_145002,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_152206,IEDB_153543,IEDB_158555,IEDB_164174,IEDB_190606,IEDB_241101,IEDB_433717,IEDB_474450,IEDB_983930,IEDB_983931,SB_163,SB_165,SB_166,SB_187,SB_192,SB_195,SB_197,SB_44,SB_67,SB_7,SB_72,SB_88

Methods: SDS-PAGE, immunoblotting, extraction, statistical analysis, flow cytometry analysis, cytokine production, purification of murine macrophages
Comments, role: structure from [ref. 21] Coelho-Finamore JM, et al., Int J Parasitol 2011, 41:333–342, DOI:10.1016/j.ijpara.2010.10.004; side chains in type-III LPG repeats, are containing up to three glucose residues, but the precise locations of the Glc side chains in the repeat unit are not known.

Related record ID(s): 8143
NCBI Taxonomy refs (TaxIDs): 5671
Show glycosyltransferases

There are too many chemically distinct structures (~4096), so only one is shown:

ALK(1-1)[%bDGlcp(1-2)%bDGlcp(1-2)%bDGlcp(1-3)[%bDGlcp(1-2)%bDGlcp(1-2)%bDGlcp(1-3)[%bDGlcp(1-2)%bDGlcp(1-2)%bDGlcp(1-3)[SUG(1-P-6)]bDGalp(1-4)aDManp(1-P-6)]bDGalp(1-4)aDManp(1-P-6)]bDGalp(1-4)aDManp(1-P-6)aDGalp(1-6)aDGalp(1-3)bDGalf(1-3)[aDGlcp(1-P-6)]aDManp(1-3)aDManp(1-4)aDGlcpN(1-6)xXmyoIno?(1-P-3)]x?Gro?

[1*]OCC(O)COP(=O)(O)O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O[C@H]1O[C@H](CO)[C@@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O[C@H]3O[C@H](COP(=O)(O)O[C@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)[C@@H](O)[C@H](O[C@@H]4O[C@@H]([C@H](O)CO)[C@H](O[C@H]5O[C@H](CO[C@H]6O[C@H](COP(=O)(O)O[C@H]7O[C@H](CO)[C@@H](O[C@@H]8O[C@H](COP(=O)(O)O[C@H]9O[C@H](CO)[C@@H](O[C@@H]%10O[C@H](COP(=O)(O)O[C@H]%11O[C@H](CO)[C@@H](O[C@@H]%12O[C@H](COP(=O)(O)O[2*])[C@H](O)[C@H](O[C@@H]%13O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%13O[C@@H]%13O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%13O[C@@H]%13O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%13O)[C@H]%12O)[C@H](O)[C@@H]%11O)[C@H](O)[C@H](O[C@@H]%11O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%11O[C@@H]%11O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%11O[C@@H]%11O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%11O)[C@H]%10O)[C@H](O)[C@@H]9O)[C@H](O)[C@H](O[C@@H]9O[C@H](CO)[C@@H](O)[C@H](O)[C@H]9O[C@@H]9O[C@H](CO)[C@@H](O)[C@H](O)[C@H]9O[C@@H]9O[C@H](CO)[C@@H](O)[C@H](O)[C@H]9O)[C@H]8O)[C@H](O)[C@@H]7O)[C@H](O)[C@H](O)[C@H]6O)[C@H](O)[C@H](O)[C@H]5O)[C@H]4O)[C@@H]3O)[C@@H]2O)[C@H](O)[C@H]1N

SVG MW SMILES 3D mol Ionize

R1 = ALK
R2 = SUG
Warning = sub-repeat ending at xXP?: unknown unit count was assumed to be 3

]; mucocutaneous leishmaniasis [ICD11: 1F54.2

, ICD11: XN8JE

]

NCBI PubMed ID: 23497381
Publication DOI: 10.1186/1756-3305-6-54
Journal NLM ID: 101462774
Publisher: London: BioMed Central
Correspondence: rsoares

cpqrr.fiocruz.br
Institutions: Centro de Pesquisas Rene Rachou, Fundacao Oswaldo Cruz - FIOCRUZ, Av, Augusto de Lima, 1715, Belo Horizonte, 30190-002, Brazil

Leishmania braziliensis, Leishmania infantum, Lipophosphoglycan (LPG), Macrophage modulation, procyclic form

Structure type: oligomer
Location inside paper: Fig. 1, LPG - type I
Compound class: LPG
Contained glycoepitopes: IEDB_130701,IEDB_134623,IEDB_134624,IEDB_136044,IEDB_136095,IEDB_136100,IEDB_136906,IEDB_137472,IEDB_141794,IEDB_141807,IEDB_142349,IEDB_142350,IEDB_142488,IEDB_144983,IEDB_144993,IEDB_144996,IEDB_144998,IEDB_145002,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_152206,IEDB_164174,IEDB_190606,IEDB_433717,IEDB_474450,IEDB_983930,IEDB_983931,SB_163,SB_165,SB_166,SB_187,SB_192,SB_195,SB_197,SB_44,SB_67,SB_7,SB_72,SB_88

Methods: SDS-PAGE, immunoblotting, extraction, statistical analysis, flow cytometry analysis, cytokine production, purification of murine macrophages
Comments, role: structure from [ref. 24] Soares RP, et al., Int J Parasitol 2005, 35:245–253, DOI:10.1016/j.ijpara.2004.12.008.

Related record ID(s): 7315
NCBI Taxonomy refs (TaxIDs): 1295825
Show glycosyltransferases

There is only one chemically distinct structure:

SVG MW SMILES 3D mol Ionize

R1 = ALK
R2 = SUG
Warning = sub-repeat ending at xXP?: unknown unit count was assumed to be 3