Abstract
Lipophosphoglycan (LPG) is the major Leishmania surface glycoconjugate having importance during the host-parasite interface. Leishmania (Viannia) braziliensis displays a spectrum of clinical forms including: typical cutaneous leishmaniasis (TL), mucocutaneous (ML), and atypical lesions (AL). Those variations in the immunopathology may be a result of intraspecies polymorphisms in the parasite's virulence factors. In this context, we evaluated the role of LPG of strains originated from patients with different clinical manifestations and the sandfly vector. Six isolates of L. braziliensis were used: M2903, RR051 and RR418 (TL), RR410 (AL), M15991 (ML), and M8401 (vector). LPGs were extracted and purified by hydrophobic interaction. Peritoneal macrophages from C57BL/6 and respective knock-outs (TLR2−/− and TLR-4−/−) were primed with IFN-γ and exposed to different LPGs for nitric oxide (NO) and cytokine production (IL-1β, IL-6, IL-12, and TNF-α). LPGs differentially activated the production of NO and cytokines via TLR4. In order to ascertain if such functional variations were related to intraspecies polymorphisms in the LPG, the purified glycoconjugates were subjected to western blot with specific LPG antibodies (CA7AE and LT22). Based on antibody reactivity preliminary variations in the repeat units were detected. To confirm these findings, LPGs were depolymerized for purification of repeat units. After thin layer chromatography, intraspecies polymorphisms were confirmed especially in the type and/size of sugars branching-off the repeat units motif. In conclusion, different isolates of L. braziliensis from different clinical forms and hosts possess polymorphisms in their LPGs that functionally affected macrophage responses.
Highlights
The Lipophosphoglycan (LPG) is the most studied glycoconjugate expressed by Leishmania
Studies with Old World Leishmania species already reported the role of LPG for the induction of cytokines, nitric oxide (NO) and MAPKs (Brittingham and Mosser, 1996; Feng et al, 1999)
L. major LPG was the first TLR2 agonist reported for human natural-killer (NK) cells and murine macrophages
Summary
The Lipophosphoglycan (LPG) is the most studied glycoconjugate expressed by Leishmania. It is a pathogen-associated molecular pattern (PAMP) covering the entire promastigote surface and flagellum and is implicated in a wide variety of events during the interaction of the parasite with vertebrate and invertebrate hosts. LPGs and glycoinositolphospholipids (GIPLs) structures from several species have been reported as important for the virulence mechanisms especially during the innate immune compartment (Becker et al, 2003; de Veer et al, 2003; Spath et al, 2003; De Assis et al, 2012). Most of the polymorphisms in the structure of LPG are located in the repeat units and cap structures. There are still uncertainties in how intraspecies structural and compositional polymorphisms of LPG affect parasite virulence
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