Abstract
The exovesicles (EVs) are involved in pathologic host-parasite immune associations and have been recently used as biomarkers for diagnosis of infectious diseases. The release of EVs by Trypanosoma cruzi, the causative agent of Chagas disease, has recently been described, with different protein cargoes including the MASP multigene family of proteins MASPs are specific to this parasite and characterized by a conserved C-terminal (C-term) region and an N-terminal codifying for a signal peptide (SP). In this investigation, we identified immature MASP proteins containing the MASP SP in EVs secreted by the infective forms of the parasite. Those EVs are responsible for the formation of immune complexes (ICs) containing anti-MASP SP IgGs in patients with different (cardiac, digestive and asymptomatic) chronic Chagas disease manifestations. Moreover, purified EVs as well as the MASP SP inhibit the action of the complement system and also show a significant association with the humoral response in patients with digestive pathologies. These findings reveal a new route for the secretion of MASP proteins in T. cruzi, which uses EVs as vehicles for immature and misfolded proteins, forming circulating immune complexes. Such complexes could be used in the prognosis of digestive pathologies of clinical forms of Chagas disease.
Highlights
Chagas disease is an endemic disease in 21 South and Central American countries, affecting around 6–7 million people worldwide[1], with 50.000 to 200.000 news cases each year[2]
Among the most antigenic proteins in T. cruzi, three multigene protein families are present on the parasite surface, namely: trans-sialidases (TSs), mucins and mucin-associated surface proteins (MASPs)[10,11], that are encoded by a large number of genes bearing repeated sequences (RSs) or sequences repeated in tandem (TRSs)[12]
We have described for the first time, the presence of a MASP signal peptide (SP) peptide in T. cruzi EVs, an alternative non-canonical pathway for SP secretion as well as the presence of an associated humoral response against this antigen region with the subsequent formation of circulating immune complexes (ICs)
Summary
Chagas disease is an endemic disease in 21 South and Central American countries, affecting around 6–7 million people worldwide[1], with 50.000 to 200.000 news cases each year[2]. During the initial phase of infection, T. cruzi is capable of evading the lysis mediated by the complement system due to the inactivation of the C3b/C4b component of alternative and classical complement pathway by direct binding to glycoproteins such as gp[160], gp58/68 and calreticulin (TcCRT) on the surface of parasite[20,21,22] All these mechanisms conclude with the progression to the chronic phase of the disease (~60 days post-infection) with an hypergammaglobulinemia increase in murine models characterized by a rise of the IgM, IgG1, IgG3 and IgG2b and IgG2a isotypes, with a predominance of the last which increases up to ten times its normal value[23,24], the presence of immune complexes (ICs) in patients with Chagas disease has been reported since the 1980s25–28. These released PMVs are capable of inactivating the classical and lectin-complement pathway avoiding the death of the parasite
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
