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.

journal_name

PLoS Negl Trop Dis

authors

Nogueira PM,Assis RR,Torrecilhas AC,Saraiva EM,Pessoa NL,Campos MA,Marialva EF,Ríos-Velasquez CM,Pessoa FA,Secundino NF,Rugani JN,Nieves E,Turco SJ,Melo MN,Soares RP

doi

10.1371/journal.pntd.0004848

subject

Has Abstract

pub_date

2016-08-10 00:00:00

pages

e0004848

issue

8

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-15-01775

journal_volume

10

pub_type

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