Differential expression of TLRs 2, 4, 9, iNOS and TNF-α and arginase activity in peripheral blood monocytes from glucantime unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis caused by Leishmania tropica.
Adolescent
Adult
Arginase
/ genetics
Case-Control Studies
Child
Child, Preschool
Down-Regulation
Female
Gene Expression
Host-Parasite Interactions
/ immunology
Humans
Iran
Leishmania tropica
/ genetics
Leishmaniasis, Cutaneous
/ immunology
Male
Meglumine Antimoniate
/ metabolism
Monocytes
/ metabolism
Nitric Oxide Synthase Type II
/ genetics
Toll-Like Receptor 10
/ genetics
Toll-Like Receptor 2
/ genetics
Toll-Like Receptor 4
/ genetics
Toll-Like Receptors
/ genetics
Tumor Necrosis Factor-alpha
/ genetics
Up-Regulation
Young Adult
Arginase level
Glucantime unresponsiveness
Inflammatory mediators
Leishmania tropica
Leishmaniasis
Toll like receptors
Journal
Microbial pathogenesis
ISSN: 1096-1208
Titre abrégé: Microb Pathog
Pays: England
ID NLM: 8606191
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
31
08
2018
revised:
29
10
2018
accepted:
02
11
2018
pubmed:
7
11
2018
medline:
5
3
2019
entrez:
7
11
2018
Statut:
ppublish
Résumé
Detection of the mechanism of host/parasite interactions in unresponsive forms of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica is helpful for immunotherapy and vaccine development. In the present study, the gene expression of toll-like receptors (TLRs), TNF-α, iNOS and also arginase (ARG) activity in monocytes from Glucantime unresponsive in comparison to responsive patients infected with L. tropica was investigated. In this case-control study, patients with unresponsive (n = 10) and responsive (n = 10) ACL were recruited. Gene expression of TLR2, TLR4, TLR9, TNF-α and iNOS was analyzed in L. tropica-exposed monocytes. The level of ARG activity in both isolated promastigotes and the lysates of monocytes was also determined. L. tropica-exposed monocytes represented higher expression of all three TLRs and TNF-α and lower expression of iNOS compared to unexposed ones in both groups of patients. Results revealed a significant down-regulation of TLR2 and TNF-α and up-regulation of TLR9 expression in unresponsive isolates in comparison to responsive ones. Besides, ARG level showed a significant increase in L. tropica-stimulated monocytes and cultured promastigotes from unresponsive isolates versus responsive ones. The decreased TLR2, TLR4, TNF-α and iNOS and the increased level of TLR9 expression in L. tropica-exposed monocytes from unresponsive isolates and also the increment in ARG activity in their promastigotes and monocytes, might possibly be involved in the severity of the disease and leading to Glucantime unresponsiveness.
Sections du résumé
BACKGROUND
BACKGROUND
Detection of the mechanism of host/parasite interactions in unresponsive forms of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica is helpful for immunotherapy and vaccine development. In the present study, the gene expression of toll-like receptors (TLRs), TNF-α, iNOS and also arginase (ARG) activity in monocytes from Glucantime unresponsive in comparison to responsive patients infected with L. tropica was investigated.
METHODS
METHODS
In this case-control study, patients with unresponsive (n = 10) and responsive (n = 10) ACL were recruited. Gene expression of TLR2, TLR4, TLR9, TNF-α and iNOS was analyzed in L. tropica-exposed monocytes. The level of ARG activity in both isolated promastigotes and the lysates of monocytes was also determined.
RESULTS
RESULTS
L. tropica-exposed monocytes represented higher expression of all three TLRs and TNF-α and lower expression of iNOS compared to unexposed ones in both groups of patients. Results revealed a significant down-regulation of TLR2 and TNF-α and up-regulation of TLR9 expression in unresponsive isolates in comparison to responsive ones. Besides, ARG level showed a significant increase in L. tropica-stimulated monocytes and cultured promastigotes from unresponsive isolates versus responsive ones.
CONCLUSIONS
CONCLUSIONS
The decreased TLR2, TLR4, TNF-α and iNOS and the increased level of TLR9 expression in L. tropica-exposed monocytes from unresponsive isolates and also the increment in ARG activity in their promastigotes and monocytes, might possibly be involved in the severity of the disease and leading to Glucantime unresponsiveness.
Identifiants
pubmed: 30399441
pii: S0882-4010(18)31510-9
doi: 10.1016/j.micpath.2018.11.004
pii:
doi:
Substances chimiques
TLR10 protein, human
0
TLR2 protein, human
0
TLR4 protein, human
0
Toll-Like Receptor 10
0
Toll-Like Receptor 2
0
Toll-Like Receptor 4
0
Toll-Like Receptors
0
Tumor Necrosis Factor-alpha
0
Meglumine Antimoniate
75G4TW236W
NOS2 protein, human
EC 1.14.13.39
Nitric Oxide Synthase Type II
EC 1.14.13.39
Arginase
EC 3.5.3.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
368-378Informations de copyright
Copyright © 2018 Elsevier Ltd. All rights reserved.