The dramatic increase in CD163 expression in HEK293 CD163-transfected cells in contrast to the untransfected cells (Fig. 5E) was reflected in a significantly higher ML uptake/internalization increase (Fig. 5F). No major difference in the percentage of infected cells was found in comparison with the transfected and untransfected HEK293 cells either 2 or 16 h postinfection. However, ML association (not shown) and uptake (Fig. 5F) were more
efficient in CD163-transfected cells than untransfected cells after 16 h of culture (9807 ± 235 ML MIF in untransfected cells versus 22811 ± 1724, p < 0.001). As a whole, these data strongly suggest that CD163 functions as an alternative Protein Tyrosine Kinase inhibitor receptor for ML entry into host cells. To verify selleck chemicals llc if CD163 is involved in iron uptake by LL cells, AFB-negative BT skin lesions (n = 6) and LL skin samples (n = 9) showing bacteriological index > 5 (Wade staining, Fig. 6A) were submitted to Perls’ Prussian blue reaction. Positive iron deposits were detected intracellularly in foamy, bacilli-loaded macrophages (Fig. 6B). In BT samples, epithelioid macrophages occupying the core of the typical tuberculoid granuloma stained completely negative (Fig. 6C). Small foci of iron deposits in vaguely differentiated macrophages were seen in BT lesions. In this study, past descriptions that foamy macrophages predominate
in LL lesions among a plethora of other macrophages were all but confirmed. Immunohistochemical analysis of polar LL lesions demonstrated that the majority of these cells were positive for CD68, CD163, and IDO. Interestingly, after 6 days of culture, CD68+CD163+IDO+ markers were identified Fossariinae in cells isolated from LL lesions, suggesting that a part of these cell populations maintains the same phenotype while simultaneously discarding their intracellular bacilli and foamy appearance. In vitro studies have demonstrated that ML provides both positive and negative regulatory signals even
when TCRs are the trigger stimuli [22]. Although live ML seems to be more efficient at inducing ML phagocytosis, heat-killed ML is more effective at inducing T-cell activation [23]. Moreover, we herein describe that CD163 scavenger receptor type 2 is induced by both live and dead ML. The increased CD163 expression triggered by ML positively correlated with IDO and CD209 expression. The role of CD163 as a bacterial receptor was first described by Fabriek et al. [16], who considered that bacterial and cellular recognition constitutes unifying and perhaps even primordial functions of the scavenger domain as well. Both the CD163 blockade and the cythocalasin B treatment were found to inhibit ML uptake by human monocytes, leading to the conjecture that CD163 contributes to ML entry into host cells and that CD163 activity is regulated by the phagocytic machinery.