Mycobacterium leprae induces a tolerogenic profile in monocyte-derived dendritic cells via TLR2 induction of IDO

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Jéssica A. P. Oliveira¹  Mariana Gandini²  Jorgenilce S. Sales¹  Sérgio K. Fujimori³  Mayara G. M. Barbosa⁴  Valber S. Frutuoso⁵  Milton O. Moraes¹  Euzenir N. Sarno¹  Maria C. V. Pessolani²  Roberta O. Pinheiro¹ 

[1] Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation;Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation;Laboratory for Development and Analytical Validation, Oswaldo Cruz Foundation, Farmanguinhos;Cascalho-Platt Laboratory, Department of Surgery, University of Michigan;Immunopharmacology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

关键词: dendritic cells;    IDO;    lepromatous leprosy;    leprosy;    Mycobacterium leprae;    reversal reaction;   

DOI  :  10.1002/JLB.4A0320-188R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 treated with 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.

【 授权许可】

CC BY