Nox complex protein expression and function is greatly affected by redox compounds, and it is especially regulated by PDI with implications for cell signalling [60] . The association of PDI to p22 phox and other Nox isoforms in different cell types, especially in vascular cells, has been previously described [60] [61] [62] . A functional and spatial/physical interaction between PDI and the p22 phox oxidase subunit was shown in macrophages [22] and more recently between PDI and p47 phox in neutrophils [62] . In macrophages, PDI-Nox association was correlated to Leishmania infection in vitro [22] . It is well known that during phagocytosis of Leishmania, Nox2 is activated and parasite uptake is inhibited by antioxidants such as catalase [22] . Intriguingly, in the course of promastigote infection, some parasites evade that stressful condition and convert themselves into intracellular amastigotes, multiplying and resulting in progression to a disease process. Overall, our studies support the view that parasite phagocytosis/infection by macrophages is a redox process mediated by PDI in at least two ways. Initially, PDI-NADPH oxidase increases ROS production generating an oxidizing milieu, which seems to favour promastigote infection. The downstream role of ROS generated by PDI-NADPH oxidase remains unknown but can be related to the unfolded protein response signalling [63] or, similar to PDI-Ero1, to protein folding in the macrophage ER compartment with key implications for antigen processing. Nevertheless, at later stages of infection, macrophage PDI physically associates with Leishmania elongation factor-2 (as discussed earlier).