title: Two biochemically distinct lipophosphoglycans from Leishmania braziliensis and Leishmania infantum trigger different innate immune responses in murine macrophages.
abstract: 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.
  
  
  CONCLUSIONS
  These data suggest that two biochemically distinct LPGs were able to differentially modulate macrophage functions.
authors.affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Av, Augusto de Lima, 1715, Belo Horizonte, 30190-002, Brazil.
authors.forename: Izabela Coimbra
authors.initials: IC
authors.lastname: Ibraim
authors.forename: Rafael Ramiro
authors.initials: RR
authors.lastname: de Assis
authors.forename: Natália Lima
authors.initials: NL
authors.lastname: Pessoa
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: Campos
authors.forename: Maria Norma
authors.initials: MN
authors.lastname: Melo
authors.forename: Salvatore Joseph
authors.initials: SJ
authors.lastname: Turco
authors.forename: Rodrigo Pedro
authors.initials: RP
authors.lastname: Soares
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006028:Glycosphingolipids / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D007892:Leishmania braziliensis / Q000276:immunology* / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology* / Q000378:metabolism; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D020935:MAP Kinase Signaling System / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009573:Nitrites / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D006028:Glycosphingolipids; D016328:NF-kappa B; D009573:Nitrites; C008290:lipophosphonoglycan