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https://www.arca.fiocruz.br/handle/icict/43527
IMMUNOMODULATORY PROPERTIES OF LEISHMANIA EXTRACELLULAR VESICLES DURING HOST-PARASITE INTERACTION: DIFFERENTIAL ACTIVATION OF TLRS AND NF-KB TRANSLOCATION BY DERMOTROPIC AND VISCEROTROPIC SPECIES
Leishmania
Interações hospedeiro-parasita
Imunidade inata
Lipofosfoglicano
Leishmania
Host-parasite interaction
Innate immunity
Lipophosphoglycan
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Université du Québec. Centre Armand-Frappier Santé Biotechnologie. Laval, QC, Canada.
Universidade Federal de São Paulo. Departamento de Ciências Farmacêuticas. Diadema, SP, Brasil.
Universidade Federal de São Paulo. Departamento de Ciências Farmacêuticas. Diadema, SP, Brasil.
Weizmann Institute of Science. Department of Biomolecular Sciences Rehovot. Israel.
Weizmann Institute of Science. Department of Biomolecular Sciences Rehovot. Israel.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Université du Québec. Centre Armand-Frappier Santé Biotechnologie. Laval, QC, Canada.
Universidade Federal de São Paulo. Departamento de Ciências Farmacêuticas. Diadema, SP, Brasil.
Universidade Federal de São Paulo. Departamento de Ciências Farmacêuticas. Diadema, SP, Brasil.
Weizmann Institute of Science. Department of Biomolecular Sciences Rehovot. Israel.
Weizmann Institute of Science. Department of Biomolecular Sciences Rehovot. Israel.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Abstract
Leishmania infection causes considerable human morbidity and may develop into a
deadly visceral form in endemic regions. The parasite infects macrophages where they
can replicate intracellularly. Furthermore, they modulate host immune responses by
using virulence factors (lipophosphoglycan, glycoprotein-63, and others) that promote
survival inside the cells. Extracellular vesicles (EVs) released by parasites are important
for cell-cell communication in the proinflammatory milieu modulating the establishment
of infection. However, information on the ability of EVs from different Leishmania species
to modulate inflammatory responses is scarce, especially from those species causing
different clinical manifestations (visceral vs. cutaneous). The purpose of this study was to
compare macrophage activation using EVs from three Leishmania species from New
World including L. infantum, L. braziliensis, and L. amazonensis. EVs were released
from promastigote forms, purified by ultracentrifugation and quantitated by Nanoparticle
Tracking Analysis (NTA) prior to murine macrophage exposure. NTA analysis did not
show any differences in the EV sizes among the strains. EVs from L. braziliensis and
L. infantum failed to induce a pro-inflammatory response. EVs from both L. infantum
WT and LPG-deficient mutant (LPG-KO) did not show any differences in their interaction
with macrophages, suggesting that LPG solely was not determinant for activation. On
the other hand, EVs from L. amazonensis were immunomodulatory inducing NO, TNF-a,
IL-6, and IL-10 via TLR4 and TLR2. To determine whether such activation was related to
NF-kB p65 translocation, THP-1 macrophage cells were exposed to EVs. In the same way, only EVs from L. amazonensis exhibited a highly percentage of cells positive for
NF-kB. Our results suggest an important role of EVs in determining the pattern of immune
response depending on the parasite species. For L. infantum, LPG was not determinant
for the activation.
Keywords in Portuguese
Vesículas extracelularesLeishmania
Interações hospedeiro-parasita
Imunidade inata
Lipofosfoglicano
Keywords
Extracellular vesiclesLeishmania
Host-parasite interaction
Innate immunity
Lipophosphoglycan
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