Abstract
The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in sugars that branch off the conserved Gal(β1,4)Man(α1)-PO4 backbone of repeat units. Here, the immunomodulatory activity of LPGs from Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis, was evaluated in two strains from Brazil. One strain (PH8) was originally isolated from the sand fly and the other (Josefa) was isolated from a human case. The ability of purified LPGs from both strains was investigated during in vitro interaction with peritoneal murine macrophages and CHO cells and in vivo infection with Lutzomyia migonei. In peritoneal murine macrophages, the LPGs from both strains activated TLR4. Both LPGs equally activate MAPKs and the NF-κB inhibitor p-IκBα, but were not able to translocate NF-κB. In vivo experiments with sand flies showed that both stains were able to sustain infection in L. migonei. A preliminary biochemical analysis indicates intraspecies variation in the LPG sugar moieties. However, they did not result in different activation profiles of the innate immune system. Also those polymorphisms did not affect infectivity to the sand fly.
Highlights
The major cell surface glycoconjugate of Leishmania is the lipophosphoglycan (LPG), implicated in a wide range of functions, both in vertebrate and invertebrate hosts [7]
Most of the mechanisms involved in L. amazonensis pathogenesis are still unknown, especially those related to surface molecules
We here present the role of lipophosphoglycan (LPG) of L. amazonensis in the interaction with vertebrate and invertebrate hosts
Summary
The major cell surface glycoconjugate of Leishmania is the lipophosphoglycan (LPG), implicated in a wide range of functions, both in vertebrate and invertebrate hosts [7]. LPG variations are important for Leishmania specificity to the sand fly [8], where attachment of the parasite to a midgut receptor is a crucial event [9]. The main functions of this virulence factor during the earlier steps of infection include: protect the parasite from complement-mediated lysis, attachment and entry into macrophages [10], able to inhibit phagolysosomal fusion [11], modulation of nitric oxide (NO) production [12] and inhibition of protein kinase C (PKC) [13]. L. amazonensis LPG is important in many steps of host infection, its role during the interaction with macrophages and sand flies remains unknown
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