Article
Immunomodulatory Properties of Leishmania Extracellular Vesicles During Host-Parasite Interaction: Differential Activation of TLRs and NF-kB Translocation by Dermotropic and Viscerotropic Species
Registro en:
NOGUEIRA, Paula Monalisa et al. Immunomodulatory Properties of Leishmania Extracellular Vesicles During Host-Parasite Interaction: Differential Activation of TLRs and NF-kB Translocation by Dermotropic and Viscerotropic Species. Frontiers in Cellular and Infection Microbiology, p. 1-9, Jul. 2020.
2235-2988
10.3389/fcimb.2020.00380
Autor
Nogueira, Paula Monalisa
Menezes Neto, Armando de
Borges, Valéria de Matos
Descoteaux, Albert
Torrecilhas, Ana Claudia
Xander, Patrícia
Revach, Or-Yam
Regev-Rudzki, Neta
Soares, Rodrigo Pedro
Resumen
FAPEMIG (Fundação
de Amparo à Pesquisa do Estado de Minas Gerais (APQ-
01100-14 and PPM-X 00102-16) and CNPq (Conselho Nacional
de Desenvolvimento Cientifico e Tecnológico) (302972/2019-
6, 405336/2017-9 and 431857/2018-0). AM-N was supported
by CAPES (Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior) (AUXPE 1526/2011). AT and PX was supported
by FAPESP (Fundação de Amparo do Estado de São Paulo
(2016-01917-3 and 2016/172454) and CNPq (302104/2019-
4). AD holds the Canada Research Chair on the Biology of
Intracellular Parasitism. 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.