Leishmania (Mundinia) species differ in glycoconjugate composition and induce variable levels of NO via TLR2 and TLR4.

Leishmania (Mundinia) species have attracted increasing attention due to their ancestral phylogenetic position, broad distribution, and ability to exploit non-sand fly vectors. However, the structure and immunomodulatory role of their surface glycoconjugates remain poorly understood. We comparatively characterized the biochemical and functional properties of glycoconjugates from representative Mundinia species during interaction with murine macrophages. Lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs) were extracted, purified, and preliminary characterized from Leishmania enriettii, L. orientalis, L. martiniquensis, and L. macropodum. Immunoblotting analysis of LPG using MG1 antibody detected different levels of glucose side chains branching-off the repeat units of Mundinia species, except L. enriettii. In contrast, GIPLs were conserved and galactosylated (suggestive of type II) by fluorophore-assisted carbohydrate electrophoresis (FACE). Structural polymorphisms were assessed in relation to nitric oxide (NO) production by murine macrophages, including TLR2- and TLR4-dependent responses. Both glycoconjugates induced variable levels of NO production via TLR4, with secondary involvement of TLR2. Although we found polymorphisms in the sugar moieties, a clear correlation between structure and activity could not be found.