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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.

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Two biochemically distinct lipophosphoglycans from Leishmania braziliensis and Leishmania infantum trigger different innate immune responses in murine macrophages