Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/16779
Type
ArticleCopyright
Restricted access
Embargo date
2030-01-01
Collections
- IOC - Artigos de Periódicos [12337]
Metadata
Show full item record
THE ROLE OF INDOLEAMINE 2, 3-DIOXYGENASE IN LEPROMATOUS LEPROSY IMMUNOSUPPRESSION
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. 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 Hanseníase. Rio de Janeiro, RJ. Brasil / National Institutes of Health. Clinical Center. Laboratory of Clinical Infectious Diseases. Bethesda, MD, USA.
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 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 Hanseníase. Rio de Janeiro, RJ. Brasil / National Institutes of Health. Clinical Center. Laboratory of Clinical Infectious Diseases. Bethesda, MD, USA.
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.
Abstract
To elucidate further the possible role of the tryptophan, rate-limiting enzyme
indoleamine 2, 3-dioxygenase (IDO) in leprosy, the distribution of IDOpositive
cells and IDO activity in the skin biopsies and sera of these patients
representing the entire spectrum of the disease were studied. An increased
number of macrophages/dendritic cells (DC–lineage IDO+ cells were found in
lepromatous (LL) compared to tuberculoid (BT) and reversal reaction (RR)
patients. IDO-positive cells showing CD68 and CD86 surface markers predominated
in LL lesions, while higher levels of IDO activity were observed in
the sera of LL versus BT patients. Tests revealed an increased IDO message in
Mycobacterium leprae-stimulated peripheral blood mononuclear cells
(PBMC) by real-time polymerase chain reaction (PCR) and increased IDO
expression in M. leprae-stimulated CD14+ cells of both healthy controls (HC)
and LL patients, as evaluated via flow cytometry. Increased M. leprae-induced
IDO–protein synthesis was also confirmed by Western blot. Based on our in
vitro studies, it was confirmed that M. leprae up-regulated IDO expression
and activity in HC and LL monocytes. Interferon (IFN)-g synergized with
M. leprae in promoting IDO expression and activity in monocytes. IDO
expression induced by both IFN-g and M. leprae was abrogated by
1-methyltryptophan (1-MT). Our data suggest that M. leprae chronic infection
activates the suppressive molecule IDO which, in turn, contributes to the
specific immunosuppression observed in LL leprosy.
Share