Antigen presentation occur through two distinct pathways. Antigen presenting cells (APCs; especially macrophages and dendritic cells; DCs) are long-lived cells that capture antigens and subsequently process and present them at the cell surface, where they are recognized by T-lymphocytes. This process provides a long-term adaptive immune response to fungi, bacteria, and parasite. After internalization by the APC, antigens pass through phagosome/lysosome vesicles, where they form complexes with MHC class II (Figure 2 ), which are recognized by helper CD4+ T lymphocytes (exogenous pathway). In contrast, self cell antigens and virus synthesized within cells (mostly non-APCs) are degraded by the proteasome in the cytosol and nucleus. In successive steps, the antigen is processed, folded, and incorporated into the MHC class I ( Figure 2 ) and the complex exposed on the cell surface, and recognized by cytotoxic CD8+ T lymphocytes (endogenous pathway). These two pathways overlap and some antigens are presented by both MHC class I and II, in a process called cross-presentation. This has been described in DCs responding to viral infection, transplant rejection, and some autoimmune diseases and cancer. Moreover, a wide range of pathogens passing or living in the phagosome such as Mycobacterium tuberculosis, Salmonella typhimurium, Toxoplasma gondii, and especially Leishmania spp and Trypanosoma cruzi are all crosspresented in association to high levels of CD8 + T cells [31] . PDI as part of the ER protein folding machinery directly regulates antigen processing of the MHC class I complex [32] [33] [34] [35] . Antigens that are degraded by peptidases and proteasome to shorter peptides in the cytosol and nucleus can be further transported to the ER through the TAP system, a transmembrane ER type of ATP-binding cassette (ABC) peptide transporter family [36] . ER-located PDI interacts with the peptide-loading complex (PCL) that efficiently promotes peptide assembly with MHC class I molecules and supporting the exit of the peptide-antigen complex from the ER [32] [33] [34] . Other PCL components include calreticulin, tapasin, ERp57 (another PDI family member), and the TAP transporter itself. Cells lacking PDI present much less peptide loading to MHC class I and the disulfide bridge between the peptide and MHC groove remains in a reduced redox state [32] . Normally, this interaction is affected by the redox exchange between PDI (predominantly oxidized) and ERp57 (predominantly reduced) [32] , a condition in which PDI favours the release of peptide-MHC class I from the PCL and the antigen-MHCI complex is exited from ER [34] . In fact, PDI-bound peptide facilitates the disassembly of the tapasin-ERp57 complex while the PDI unbound to the complex is unable to interact with tapasin-ERp57, retaining MHC I molecules in the ER [34] . Overall, PDI redox activity modulates the stability of the antigen peptide-MHC class I complex and further determines the transport of the complex to the plasma membrane [32] [33] [34] [35] . These redox effects may vary according to the type of antigen and some pathogens interfere with this pathway to escape antigen process and evading CD8 + T-cells recognition. This is the case for US3 protein from human cytomegalovirus, which enhances PDI degradation via the proteasome [32] . PDI participation in immune response, however, goes beyond its role in the ER protein folding machinery and it acts at other cellular steps of host-pathogen interaction. PDI in the ER is also thought to play a role in parasite phagocytosis, and the PDI displayed on the cell surface can mediate the entry of some viral, bacterial, and protozoan. PDI is also implicated in protein unfolding and trafficking of some pathogenic antigens across the endoplasmic reticulum and towards the cytosol by the endoplasmic reticulum-associated degradation system (ERAD). This is the main pathway where proteins are retrotranslocated from the ER to cytosol and further degradated by the proteasome. Next, we discuss some examples of the cellular association between host PDI and different pathogens.