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.

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Notes/Citation Information

Published in PLOS Neglected Tropical Diseases, v. 10, no. 8, e0004848, p. 1-17.

© 2016 Nogueira et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Funding Information

This manuscript was mainly funded by Conselho Nacional de Pesquisa e Desenvolvimento of Brazil (CNPq PAPES VI 407438/2012-2; 407687/2012-2; 407743/2012; 168260/2014-0; and CNPq PROEP 401975/2012) and Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, PPM-00163-14).

journal.pntd.0004848.s001.TIF (183 kB)
S1 Fig. Growth curves of L. amazonensis.

journal.pntd.0004848.s002.TIF (91 kB)
S2 Fig. Dot-blots of Leishmania LPGs using different mAb antibodies.

journal.pntd.0004848.s003.TIF (104 kB)
S3 Fig. Cytokine production by IFN-γ primed macrophages stimulated with LPG and live parasites.