Despite limited knowledge about this traffic, it is possible that PDI exits the ER through the translocon Sec61 pore and/or via secretory vesicles [17] . PDI is thought to attach to lipids, glycans, and integral membrane proteins via electrostatic interactions at the cell plasma membrane [14, 15] , where its reductive activity mediates the infection of different pathogens ( Figure 2 , discussed later). PDI along with ERp57 have been found in the nuclei in association to DNA and affecting transcriptional activity of NF-kb, AP-1, and STAT3 [15] . These transcriptional regulators are key elements in many inflammatory processes, but their functional association to PDI and to different pathogen still elusive. In contrast to many other members of its family, such as thioredoxin itself and Erp57, PDI is not normally found in the cytosol, where it is likely cleaved by caspase-3 and -7 [18] . Protozoans and bacteria have their own PDIs ( Table 1 ). The function of these PDIs in protein folding is poorly understood; however, there are intriguing data correlating PDI expression and the pathogenicity of several parasites, especially obligatory intracellular protozoans. Leishmania that leads to distinct types [20] . If L. chagasi is a subgroup of L. infantum brought to America by European colonist or other specie in its own still a matter of controversy (see discussion in [21] ). The infection cycle in the vertebrate host and is initiated when Leishmania promastigote is injected into the skin by the insect vector. In the host, the promastigote is phagocytised especially by macrophages, and further it is converted into intracellular amastigote. Amastigote replicates inside the phagosome within the cell and is liberated after the cell lyses, subsequently infecting other cells resulting in the progression to disease [21, 22] . L. amazonensis has at least four PDIs, and the use of specific PDI inhibitors substantially affected parasite growth [23] . In L. major, the increased levels of Leishmania PDI (LmPDI) expression and secretion at the parasite surface reflects optimal protein folding balanced to parasite multiplication. Importantly, this is correlated to high virulence of the parasite strains [16] . More recently, the use of LmPDI antigens to generate a vaccine for L. major partially protected BALB/c animals and accelerated the cure of different strains of mice [24] . Similarly to Leishmania species, other parasites of the trypanosomatid group such as Trypanosoma contain several genes predicted to encode for PDIs, that can execute N-glycosylation and protein folding in the ER [25, 26] . Although PDI was considered essential for T. brucei survival, PDI activity was not essential for the growth of trypanosomes in vitro [26] . PDI is also expressed in different species of Plasmodium protozoans (Table 1) , the parasites that cause malaria [27, 28] . P. falciparum expresses at least nine different PDIs and the PfPDI-8 has great similarity to the prototype PDI and is expressed during all stages of parasite life cycle. This PDI facilitates the disulfide-dependent conformational folding of EBA-175 protein, an emerging candidate for the development of malaria vaccines [28] . This is intriguing given that malaria parasites express proteins with high content of cysteine, which are associated to parasite invasion and sequestration in the vertebrate host and transmission into mosquito host [28] . Finally, Toxoplasma gondii PDI was identified in host tears, suggesting an extracellular location and adhesion to host cells during the initial phase of infection [29] .