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https://www.arca.fiocruz.br/handle/icict/46111
MYCOBACTERIUM LEPRAE INDUCES A TOLEROGENIC PROFILE IN MONOCYTE-DERIVED DENDRITIC CELLS VIA TLR2 INDUCTION OF IDO
Células dendríticas
Lepra lepromatosa
Reação de reversão
Hanseníase
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Desenvolvimento e Validação Analítica. Rio de Janeiro, RJ, Brasil.
Cascalho-Platt Laboratory, Department of Surgery, University of Michigan. Ann Arbor, Michigan, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Desenvolvimento e Validação Analítica. Rio de Janeiro, RJ, Brasil.
Cascalho-Platt Laboratory, Department of Surgery, University of Michigan. Ann Arbor, Michigan, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
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.
Keywords in Portuguese
Mycobacterium lepraeCélulas dendríticas
Lepra lepromatosa
Reação de reversão
Hanseníase
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