Echinococcus granulosus exosome-like vesicles contain immunomodulatory and laminated layer-interacting proteins

NICOLAO, MARÍA CELESTE; RODRIGUEZ RODRIGUES, CHRISTIAN; CUMINO, ANDREA C.

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica (SAIC)

The secretion of extracellular vesicles (EVs) in helminth parasites is a constitutive mechanism that promotes survival by improving their colonization and adaptation in the host tissue. In this study, we isolated and characterized the EVs produced in cultures of E. granulosus protoscoleces and metacestodes and analyzed their biological function after contact with host cells. Similarly to that observed by TEM in protoscolex cultures, the supernatants of metacestode cultures were enriched in exosome-like vesicles. It is known that a true exchange of macromolecules across of the laminated layer occurs between the host and the parasite, with constant vesicular trafficking through the tegument. This movement may depend on signature organellar targeting motifs within the proteins and on their interactions with certain components of the laminated layer. Interestingly, the laminated layer of E. granulosus possesses deposits of the calcium salt of inositol hexakisphosphate which have been reported to bind to numerous proteins present in E. granulosus EVs (such as synaptogmins, ATP-dependent RNA helicases, pleckstrin, ezrin/radixin/moesin, gelsolin and galectin) acting as a ?dynamic anchorage? that promotes their passage across the laminated layer. Also, it is widely known that EVs derived from helminth parasites, mediate the immune modulation through their protein-, lipid- and RNAs-cargo. We strikingly found that the exposure of dendritic cells (DCs) to EVs induced an unconventional activation profile with MHCII decrease. Based on mass spectrometry analysis and in silico functional categorization, we identified: a putative immunomodulatory protein similar to the human B-Cell Receptor Associated Protein 29 (Bp29); basigin (EMMPRIN- or CD147); a maspardin ortholog (MAST or ACP33 protein) and annexins, which could explain the type 2 immune response observed in patients with cystic echinococcosis. In conclusion, our study demonstrated an important role of EVs in the maturation process of DCs which are essential for the coordination of specific immune responses.