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Open Access Research

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

Izabela Coimbra Ibraim1, Rafael Ramiro de Assis1, Natália Lima Pessoa1, Marco Antônio Campos1, Maria Norma Melo2, Salvatore Joseph Turco3 and Rodrigo Pedro Soares1*

Author Affiliations

1 Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Av. Augusto de Lima, 1715, Belo Horizonte, 30190-002, Brazil

2 Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

3 Department of Biochemistry, University of Kentucky Medical Center, Lexington, KY, USA

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Parasites & Vectors 2013, 6:54  doi:10.1186/1756-3305-6-54

Published: 7 March 2013

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.

Conclusion

These data suggest that two biochemically distinct LPGs were able to differentially modulate macrophage functions.

Keywords:
Leishmania infantum; Leishmania braziliensis; Lipophosphoglycan (LPG); Macrophage modulation