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

Publication date: Available online 3 July 2017
Source:Microbes and Infection
Author(s): Mayara Garcia de Mattos Barbosa, Rhana Berto da Silva Prata, Priscila Ribeiro Andrade, Helen Ferreira, Bruno Jorge de Andrade Silva, Jéssica Araújo da Paixão de Oliveira, Tayná Quintella Assis, Thiago Gomes de Toledo-Pinto, Ohanna Cavalcanti de Lima Bezerra, José Augusto da Costa Nery, Patricia Sammarco Rosa, Marcelo Torres Bozza, Flávio Alves Lara, Milton Ozório Moraes, Veronica Schmitz, Euzenir Nunes Sarno, Roberta Olmo Pinheiro
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 maintainance of M. leprae in host cells.



http://ift.tt/2tFvySr