02012nas a2200289   4500000000100000008004100001100001600042700001400058700001400072700001500086700002100101700002700122700001300149700002000162700002000182700001800202700001100220700001300231700001100244700001300255700001400268700001200282700001500294245008900309520131000398022001401708       2017                            d1 aBarbosa MGM1 aPrata RBS1 aAndrade P1 aFerreira H1 aAndrade Silva BJ1 aPaixão de Oliveira JA1 aAssis TQ1 aToledo-Pinto TG1 aLima Bezerra OC1 aCosta Nery JA1 aRosa P1 aBozza MT1 aLara F1 aMoraes M1 aSchmitz V1 aSarno E1 aPinheiro R00aIndoleamine 2,3-dioxygenase and iron are required for Mycobacterium leprae survival.3 a<p>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.</p>
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