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

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.

Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2

“…Early studies using synthetic Leishmania PGs demonstrated the effect of this glycoconjugate in subverting IL-12 production via the ERK pathway 49 . Later, LPG-induced MAPKs were investigated in other New World Leishmania species 17 , 21 . The ability of LPGs to induce MAPKs is variable, and is perhaps species-specific.…”

“…L . amazonensis LPGs have been reported to induce NO, TNF-α and IL-6 via TLR4 and but were not capable of translocating NF-kB 17 .…”

Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis

“…The major pathogen associated molecular pattern (PAMP) in Leishmania is lipophosphoglycan (LPG) [9]. In case of L. braziliensis [10] and L. amazonensis [11], their LPG can be recognized by Toll-like receptor (TLR) 2 and TLR4, respectively. Toll-like receptors (TLRs), Ctype lectin receptors (CLR) dectin-1 and mannose receptor (MR), complement receptors CR1 and CR3, Fc receptors and NOD-like receptor (NLR) have been reported as important for Leishmania-host interface [12][13][14].…”

Chicken eggs as a surveillance tool for malaria and leishmaniasis vector presence

“…A second group was exposed to bites from the phlebotomine species Migonemyia migonei, a vector of cutaneous leishmaniases. Both sand fly species are permissive vectors for several Leishmania species 8 . A third group of chickens was exposed to bites from Anopheles aquasalis, a vector of Plasmodium vivax and P. falciparum 9 .…”