Although not yet reported as being secreted in Trypanosoma, all four enzymes are secreted by other organisms and may be involved in functions unrelated to glycolysis, such as peptide cleavage or immunosuppressive activity [60–63]. Therefore, it cannot be excluded that Trypanosoma might use part of its energy metabolism machinery for alternative purposes. Enzymes involved in signaling constitute another group Vorinostat price of proteins identified in the T. brucei secretome (26 accessions), and some could also play physiopathological roles. Two notable examples here concern calreticulin (CRT) and prostaglandin F (PGF)

synthase. Autoantibodies against CRT are found in the sera of human hosts of a number of parasitic diseases [64] and it was suggested that the parasite-derived CRT could trigger an inappropriate immune response against self-antigens through molecular mimicry [65]. The gene encoding PGF synthase is present in T. brucei, and we show that this enzyme can be secreted. Given that African trypanosomiasis is characterized by miscarriage, due to PGF overproduction correlated with parasitemia peaks [66], the finding that T. brucei secretes a PGF synthase suggests that this enzyme may well play a role in pathogenesis. One trivial role of protein secretion in hosts is usually associated with trophic purposes for the benefit of the parasites. Several recent proteomics studies highlighted other CRT0066101 features, depending on the parasite.

For instance, whereas for Brugia malayi a large fraction of the 80 proteins found to be secreted are involved in energy metabolism [67], for the helminth Schistosoma mansoni the 188 proteins identified include proteins involved in metabolic pathways and in protein folding, development, and signaling, or immune response modulation [68], and the secretome Phosphatidylethanolamine N-methyltransferase of Plasmodium falciparum

is predicted to encompass several hundred proteins to both import nutrients and remodel the host erythrocyte [69]. In this work, the 444 identified T. brucei-secreted proteins display a specific pattern and, for a number of these, there is evidence for possible alternative functions. The various examples detailed above support the hypothesis that, far from being fortuitous, these features probably reveal an additional role for the secretome in manipulating the host in order to overcome its defenses. As such, the secretome would also play a key role in the pathogenicity of the parasite. More generally, this suggests that, apart from the production of VSGs to elude the host immune system, the secretome might also be another authentic component of the survival strategy of Trypanosoma. Origin and significance of the identified secretome for the survival strategy of Trypanosoma Only a minority of ESPs appear to possess a transit peptide, raising the question of the nature of the secretory pathway in Trypanosoma. Several arguments support the hypothesis that secretion could take place by the release of microvesicles.