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

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 irradiatedMycobacterium lepraeand its fractions.M. lepraeand its fractions induced the expression and activity of IDO-1 in human mDCs. Among the stimuli studied, irradiatedM. lepraeand its membrane fraction (MLMA) induced the production of proinflammatory cytokines TNF and IL-6 whereas irradiatedM. lepraeand 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 byM. lepraeand 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 thatM. lepraeconstituents 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 thatM. lepraeand 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.