Iron Acquisition by M. tb
Macrophages acquire iron primarily from two sources. One source is from the heme released due to the recycling of effete erythrocytes. In addition, they also acquire iron via the receptor-mediated endocytosis of transferrin (Gkouvatsos et al. 2012) and lactoferrin (Adlerova et al. 2008). Transferrin iron uptake by receptor-mediated endocytosis is a well-defined mechanism in mammalian cells. Two transmembrane transferrin receptors (TfR1 and TfR2) had previously been identified in mammalian cells (Jandl et al. 1959; Kawabata et al. 1999; West et al. 2000; Mayle et al. 2012). In this process, holo-transferrin binds to cell-surface transferrin receptors followed by subsequent internalization into the cell. Acidification of the early endosome results in the release of iron and the residual apo-transferrin complex re-cycles back to the cell surface.
In order to contain an infection, macrophages downregulate the expression of transferrin receptors to limit the entry of iron into the cell (Olakanmi et al. 2002). The host may also synthesize molecules known as siderocalins that sequester the bacterial siderophores and thereby inhibit the uptake of iron by the pathogen (Holmes et al. 2005). To evade the withholding strategies of the host iron, M. tb utilizes multiple mechanisms to appropriate host iron. These include use of siderophores (Ratledge 2004), heme capture (Tullius et al. 2011), and the recruitment of transferrin and lactoferrin to the phagosome (Olakanmi et al. 2002, 2004).