Indoleamine 2,3-dioxygenase and iron are required for Mycobacterium leprae survival.

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TitleIndoleamine 2,3-dioxygenase and iron are required for Mycobacterium leprae survival.
Publication TypeJournal Article
Authorsde Mattos Barbosa MG, da Silva Prata RB, Andrade PR, Ferreira H, de Andrade Silva BJ, da Paixão de Oliveira JA, Assis TQ, de Toledo-Pinto TG, de Lima Bezerra OC, da Costa Nery JA, Rosa PS, Bozza MT, Lara FA, Moraes MO, Schmitz V, Sarno EN, Pinheiro RO
Abbrev. JournalMicrobes Infect.
JournalMicrobes and infection
Year of Publication2017
Publication Languageeng

Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO4 stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the baciloscopic index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells.

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