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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)-PO 4  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.

Lipophosphoglycans from Leishmania amazonensis Strains Display Immunomodulatory Properties via TLR4 and Do Not Affect Sand Fly Infection