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

• Published in: Microbes and infection 2017-11, Vol.19 (11), p.505-514
• Main Authors: de Mattos Barbosa, Mayara Garcia, da Silva Prata, Rhana Berto, Andrade, Priscila Ribeiro, Ferreira, Helen, de Andrade Silva, Bruno Jorge, da Paixão de Oliveira, Jéssica Araújo, Assis, Tayná Quintella, de Toledo-Pinto, Thiago Gomes, de Lima Bezerra, Ohanna Cavalcanti, da Costa Nery, José Augusto, Rosa, Patricia Sammarco, Bozza, Marcelo Torres, Lara, Flávio Alves, Moraes, Milton Ozório, Schmitz, Veronica, Sarno, Euzenir Nunes, Pinheiro, Roberta Olmo
• Format: Article
• Language: English
• Subjects: Adult; Female; Humans; Immunoblotting; Immunoenzyme Techniques; Indoleamine 2,3-dioxygenase; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Indoleamine-Pyrrole 2,3,-Dioxygenase - physiology; Iron; Iron - metabolism; Iron - physiology; Leprosy; Leprosy, Lepromatous - metabolism; Leprosy, Lepromatous - microbiology; Macrophages; Male; Middle Aged; Mycobacterium leprae; Mycobacterium leprae - metabolism; Mycobacterium leprae - physiology; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2017.06.006

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 bacillary 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.