Characterization of exosome-like vesicles during drug treatment of cyst echinococcosis

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

Mar del Plata

Congreso; Reunión Anual de las Sociedades de Biociencia 2019. SAIC, SAFE, SAB, SAP, AACYTAL, NANOMED-ar, HCS; 2019

Cystic echinococcosis (CE) is a chronic zoonotic disease which shows a high prevalence in Argentina (Patagonia, Catamarca, Santiago del Estero, Salta and Entre Ríos) caused by Echinococcus granulosus larval cystic stage. Humans acquire the disease by ingestion of cestode eggs from contaminated soil or food. As other parasite helminths, E. granulosus adopt complex strategies of communication with their hosts, driving a physiological and immunological homeostasis to achieve long-term parasitism. Our attention has been focused in the exosome-like vesicles (EVs) and their importance in cellular crosstalk under drug treatment pressure. Previously, we characterized EVs from protoscoleces and metacestodes, and demonstrated for the first time that they interact with host dendritic cells inducing an unconventional activation profile with MHCII decrease. EVs were characterized by dynamic light scattering and proteomic analysis from control, metformin- and albendazole-treated parasite cultures. This allowed us to identify at least twenty small molecular weight antigenic proteins, which showed constant proportion between samples with and without pharmacological treatment. Amongst them, two unknown antigens (W6UFE0 and U6IZE6) were identified. Interestingly, drug treatment led to a decrease in tolerogenic proteins and certain extracellular matrix-interacting and epithelial-mesenchymal transition inducing proteins. These findings could be correlated to the effectiveness of the pharmacological treatment described in murine models and patients for metformin and albendazol, respectively. More precisely, it is known that albendazole-treatment increase the Th1 cytokine profile, indicating that Th1 responses play a role in the process of cyst degeneration. Here, we provide valuable data on the occurrence of cargo proteins that can promote proliferation, induce dissemination and evade immune response in the parasite-host interface. Currently we are engaged in selecting proteins with potential applications as immunosuppressive drugs.