Geiger Anne auteur aut IRD Hirtz C. auteur aut IRD Becue T. auteur aut IRD Bellard E. auteur aut IRD Centeno D. auteur aut IRD Gargani D. auteur aut IRD Rossignol M. auteur aut IRD Cuny Gérard auteur aut IRD Peltier J. B. auteur aut IRD text journalArticle eng text/pdf reformatted digital access Background: Human African trypanosomiasis is a lethal disease caused by the extracellular parasite Trypanosoma brucei. The proteins secreted by T. brucei inhibit the maturation of dendritic cells and their ability to induce lymphocytic allogenic responses. To better understand the pathogenic process, we combined different approaches to characterize these secreted proteins. Results: Overall, 444 proteins were identified using mass spectrometry, the largest parasite secretome described to date. Functional analysis of these proteins revealed a strong bias toward folding and degradation processes and to a lesser extent toward nucleotide metabolism. These features were shared by different strains of T. brucei, but distinguished the secretome from published T. brucei whole proteome or glycosome. In addition, several proteins had not been previously described in Trypanosoma and some constitute novel potential therapeutic targets or diagnostic markers. Interestingly, a high proportion of these secreted proteins are known to have alternative roles once secreted. Furthermore, bioinformatic analysis showed that a significant proportion of proteins in the secretome lack transit peptide and are probably not secreted through the classical sorting pathway. Membrane vesicles from secretion buffer and infested rat serum were purified on sucrose gradient and electron microscopy pictures have shown 50- to 100-nm vesicles budding from the coated plasma membrane. Mass spectrometry confirmed the presence of Trypanosoma proteins in these microvesicles, showing that an active exocytosis might occur beyond the flagellar pocket. Conclusions: This study brings out several unexpected features of the secreted proteins and opens novel perspectives concerning the survival strategy of Trypanosoma as well as possible ways to control the disease. In addition, concordant lines of evidence support the original hypothesis of the involvement of microvesicle-like bodies in the survival strategy allowing Trypanosoma to exchange proteins at least between parasites and/or to manipulate the host immune system. specialized AFRIQUE SUBSAHARIENNE 052 10 20 2010 1471-2180 https://www.documentation.ird.fr/hor/fdi:010049354 10.1186/1471-2180-10-20 1471-2180 [F B010049354] https://www.documentation.ird.fr/hor/fdi:010049354 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers17-09/010049354.pdf IRD - Base Horizon / Pleins textes 2010-04-06 2020-03-17 fdi:010049354 fre