Author | Oliveira, Jéssica A. P. | |
Author | Gandini, Mariana | |
Author | Sales, Jorgenilce S. | |
Author | Fujimori, Sérgio K. | |
Author | Barbosa, Mayara G. M. | |
Author | Frutuoso, Valber S. | |
Author | Moraes, Milton Ozório | |
Author | Sarno, Euzenir N. | |
Author | Pessolani, Maria C. V. | |
Author | Pinheiro, Roberta O. | |
Access date | 2021-02-19T19:09:31Z | |
Available date | 2021-02-19T19:09:31Z | |
Document date | 2020 | |
Citation | OLIVEIRA, Jéssica A. P. et al. Mycobacterium leprae induces a tolerogenic profile in monocyte-derived dendritic cells via TLR2 induction of IDO. Journal of Leukocyte Biology, 2020, p. 1-10, Sept. 2020. | pt_BR |
ISSN | 0741-5400 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/46111 | |
Language | eng | pt_BR |
Publisher | Wiley | pt_BR |
Rights | open access | |
Subject in Portuguese | Mycobacterium leprae | pt_BR |
Subject in Portuguese | Células dendríticas | pt_BR |
Subject in Portuguese | Lepra lepromatosa | pt_BR |
Subject in Portuguese | Reação de reversão | pt_BR |
Subject in Portuguese | Hanseníase | pt_BR |
Title | Mycobacterium leprae induces a tolerogenic profile in monocyte-derived dendritic cells via TLR2 induction of IDO | pt_BR |
Type | Article | |
DOI | 10.1002/JLB.4A0320-188R | |
Abstract | The enzyme IDO-1 is involved in the first stage of tryptophan catabolism and has been described in
both microbicidal and tolerogenic microenvironments. Previous data from our group have shown
that IDO-1 is differentially regulated in the distinctive clinical forms of leprosy. The present study
aims to investigate the mechanisms associated with IDO-1 expression and activity in human
monocyte-derived dendritic cells (mDCs) after stimulation with irradiated Mycobacterium leprae
and its fractions. M. leprae and its fractions induced the expression and activity of IDO-1 in human
mDCs. Among the stimuli studied, irradiated M. leprae and its membrane fraction (MLMA) induced
the production of proinflammatory cytokines TNF and IL-6 whereas irradiated M. leprae and its
cytosol fraction (MLSA) induced an increase in IL-10.We investigated if TLR2 activation was necessary
for IDO-1 induction in mDCs.We observed that in cultures treatedwith a neutralizing anti-
TLR2 antibody, there was a decrease in IDO-1 activity and expression induced by M. leprae and
MLMA. The same effect was observed when we used a MyD88 inhibitor. Our data demonstrate
that coculture of mDCs with autologous lymphocytes induced an increase in regulatory T (Treg)
cell frequency in MLSA-stimulated cultures, showing that M. leprae constituents may play opposite
roles that may possibly be related to the dubious effect of IDO-1 in the different clinical forms
of disease. Our data show that M. leprae and its fractions are able to differentially modulate the
activity and functionality of IDO-1 in mDCs by a pathway that involves TLR2, suggesting that this
enzyme may play an important role in leprosy immunopathogenesis. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Desenvolvimento e Validação Analítica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Cascalho-Platt Laboratory, Department of Surgery, University of Michigan. Ann Arbor, Michigan, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Dendritic cells | pt_BR |
Subject | IDO | pt_BR |
Subject | Lepromatous leprosy | pt_BR |
Subject | Leprosy | pt_BR |
Subject | Mycobacterium leprae | pt_BR |
Subject | Reversal reaction | pt_BR |
DeCS | Indolamina-Pirrol 2,3,-Dioxigenase | pt_BR |