Phagocytosis is the main gate for large microbes to enter into APCs. After binding and attaching to the pathogen, these cells can internalize organisms and large particles even bigger then their own size, which are then phagocytosed in an active process that involves intense membrane remodelling [37] . Proteomics studies accumulated over the last decade revealed the presence of ER chaperones in the isolated phagosome, uncovering a process called ER-mediated phagocytosis [38] [39] [40] [41] [42] [43] [44] [45] . ER chaperones were detected in phagosomes of macrophages exposed to different particulate material and pathogens, including latexbeads opsonised or not with immunoglobulin G (IgG) or mouse serum (to facilitate entry through the FcR or complement receptors), IgG-opsonized erythrocytes, promastigotes of Leishmania donovani derived from wild-type cells or cell-surface LPG knockout, among other parasites [38] . A mix of ER and endocytic vesicles in the formation of the parasitophorous vacuoles (PVs) during the uptake of different Leishmania spp. was recently shown in macrophages overexpressing ER-tagged green fluorescent protein [41] . The presence of the ER proteins Sec61, Bip/Grp78, and PDI in the phagosome of APCs [38, 41] support the idea that the ER provides the necessary machinery for antigen translocation from the phagosome to the cytoplasm and thus, possibly converges MHC class I and class II antigen cross-presentation [42] (Figure 2 ). There are several other complementary hypotheses on how peptides cross from phagosomes to cytoplasm during the cross-presentation process [43, 44] . Neutrophils are short-lived cells (half-life of 4-8 h in the human circulation) and very active in the phagocytosis of large microbes such as bacteria, parasites, and fungus. Contrary to APCs, neutrophils only contain restricted amounts of ER machinery and are thought to lack the ER-mediated phagocytosis process [38] .