Iron homeostasis is essential to the sustenance of survival and growth of host mycobacteria [32]. Both ML and M. tuberculosis produce bacterioferritins [33, 34], which could be involved in controlling iron homeostasis in these pathogens. Because CD163 is related to Hb clearance, it can be speculated that, in parasitized cells, high CD163 expression may function as a pathway for the supply of iron, which perhaps reflect some of the dissimilarities among the survival mechanisms used by the various mycobacteria. An example is the fact that whereas human Hb is not used

INCB024360 in vivo as an iron source by M. tuberculosis, it may be used for this purpose by M. haemophilum and ML [35]. In the present work, we verified larger iron storage in LL skin biopsies than in tuberculoid ones. Of note, high amounts of iron were only found in LL macrophages and none was detected in epithelioid macrophages whereas small foci of iron deposits in vaguely differentiated macrophages were seen in BT lesions. With reference to a previous description of the accumulation of lipid droplets in LL lesions [36], we could infer that ML associates with lipid vesicles as a mechanism for transferring iron from the host to ML-rich phagosomes. As a whole, our results seem to clearly suggest that, on

the one hand, CD163 may contribute to polarize LL macrophages STA-9090 to an anti-inflammatory phenotype by increasing the expression and levels of the immunoregulatory molecules IL-10 and IDO, although the other primary determinants of polarity in leprosy immune responses need to be better understood. In addition CD163 also contributes to ML uptake and increased amounts eltoprazine of iron, thus favoring bacterial survival and persistence. The acquisition of all specimens was approved by the Human Ethics Committee of the Oswaldo Cruz Foundation in Brazil. Leprosy patients (LL, n = 11 and BT, n = 10) were classified according to Ridley and Jopling

criteria [37]. Buffy coats were obtained from healthy donors (HC) at the Hemotherapy Service of the Clementino Fraga Filho University Hospital, associated with the Federal University of Rio de Janeiro, RJ, Brazil, in accordance with the guidelines set down in the Declaration of Helsinki. The leprosy skin cryostat sections (LL, n = 6 and BT, n = 6) were processed to detect IDO+ and CD163+ cells by immunoperoxidase labeling. Sections were then incubated with polyclonal anti-IDO (Santa Cruz Biotechnology, Santa Cruz, CA, USA (H-110), 1: 50) and anti-CD163 (Santa Cruz Biotechnology (sc-20066), 1: 25). Immunohistochemical staining was performed, as previously demonstrated by De Souza Sales et al. [6].