Whether ER proteins functionally operate on phagocytosis-mediated infection has not been well characterised yet. An important work has shown that Dictyostelium lacking both ER calreticulin and calnexin present altered phagocytic cup formation and substantial decline in phagocytosis [45] . These two proteins utilise Ca, and their disruption per se affects actin filaments and plasma membrane remodelling during phagocytosis [45] . We recently showed that PDI is critically involved in Leishmania parasite infection in vitro [22] . We showed that phagocytosis of promastigotes (but not amastigotes) of Leishmania chagasi was significantly inhibited by macrophage incubation with the thiol/PDI inhibitors DTNB, bacitracin, phenylarsine oxide, and neutralizing PDI antibody in a parasite redox-dependent way [22] . The phenylarsine response is of particular interest, since this arsenic compound may act similarly to antimonials, widely used in leishmaniasis chemotherapy [46, 47] . PDI preferentially affects parasite internalization and the phagocytosis of the promastigote forms is increased when wild-type PDI is overexpressed in macrophages, an effect opposed by PDI knockdown. At later stages of infection (i.e., after 4 h), PDI from promastigote-infected J774 macrophages was immunoprecipitated and subsequently blotted with an anti-Leishmania antibody revealing a parasite band at ∼ 94 KDa [16, Figure 10 (b), lane 5]. Subsequent removal and analysis of this band by mass fingerprint spectrometry showed a 58% match with elongation factor 2 (EF2) of L. major (Q4Q259; data not shown). The incubation of purified bovine PDI (Sigma, P3818) and parasites did not yield any detectable protein complexes, suggesting that the macrophage milieu may be important to sustain PDI-EF2 association [22] . Interestingly, Leishmania EF2 has important virulent features and acts as a soluble antigen in lymphocyte stimulation in vitro [48] and in vivo [49] . Moreover, proteomics studies revealed that EF2 is secreted during promastigote differentiation into the amastigote stage with potential immunomodulatory proprieties in animal models [50] . Leishmania EF2 is therefore of particular interest for Leishmania therapeutic interventions such as vaccines. Although our studies did not address the role of the ER in mediating phagocytosis, these data provide compelling evidence for a functional role of ER-PDI in a host-parasite interaction. Other mechanisms underlining PDI-mediated L. chagasi promastigote phagocytosis involves its association to ROS production by phagocyte NADPH oxidase and this is discussed next.