Exosomes from Taenia solium cysticerci impairs PI3K-AKT-mTOR pathway and induces apoptosis in macrophages

Abstract

Abstract Exosomes are extracellular vesicles of 30-100nm which constitutes significant part of secretome. Excretory secretory proteome plays significant role in pathogenesis and immune escapes mechanisms of complex parasites like Taenia solium. The cyst of T. solium causes infection to CNS i.e., neurocysticercosis (NCC) a neglected tropical disease. However, the role of exosomes in NCC pathogenesis is not understood till now. Here for the first time, we report exosomes- induce AKT degradation in macrophages via the autophagosomal-lysosomal pathway but not via the proteasomal pathway. The phenotype is supported by the low ROS production with impaired bacterial killing. Along with this PI3K pathway was also seen to be impaired after exosome stimulation in macrophages. We also found mTOR degradation was via the lysosomal pathway with a notable increase in the ubiquitination. Following this autophagy and apoptosis both increased with significant degradation of autophagy substrate SQSTM1. In summary, here we report that the T. solium exosomes modulate PI3K-AKT-mTOR pathway to induce autophagy and apoptosis in macrophages and this may exert immunosuppression via the exosomes during NCC disease. These finding helps us to understand the immune suppression induced by cyst for its survival in host.