Hydatid fluid from Echinococcus granulosus induces autophagy in dendritic cells and promotes polyfunctional T-cell responses

CHOP, MAIA; LEDO, CAMILA; NICOLAO, MARÍA CELESTE; LOOS, JULIA; CUMINO, ANDREA; RODRIGUEZ RODRIGUES, CHRISTIAN

Frontiers in Cellular and Infection Microbiology

Frontiers Media S.A.

Año: 2024 vol. 14

Parasites possess remarkable abilities to evade and manipulate the immune responseof their hosts. Echinococcus granulosus is a parasitic tapeworm that causes cysticechinococcosis in animals and humans. The hydatid fluid released by the parasite isknown to contain various immunomodulatory components that manipulate host´sdefense mechanism. In this study, we focused on understanding the effect of hydatidfluid on dendritic cells and its impact on autophagy induction and subsequent T cellresponses. Initially, we observed a marked downregulation of two C-type lectinreceptors in the cell membrane, CLEC9A and CD205 and an increase in lysosomalactivity, suggesting an active cellular response to hydatid fluid. Subsequently, wevisualized ultrastructural changes in stimulated dendritic cells, revealing the presenceof macroautophagy, characterized by the formation of autophagosomes,phagophores, and phagolysosomes in the cell cytoplasm. To further elucidate theunderlying molecular mechanisms involved in hydatid fluid-induced autophagy, weanalyzed the expression of autophagy-related genes in stimulated dendritic cells.Our results demonstrated a significant upregulation of beclin-1, atg16l1 and atg12,indicating the induction of autophagy machinery in response to hydatid fluidexposure. Additionally, using confocal microscopy, we observed an accumulationof LC3 in dendritic cell autophagosomes, confirming the activation of this catabolicpathway associated with antigen presentation. Finally, to evaluate the functionalconsequences of hydatid fluid-induced autophagy in DCs, we evaluated cytokinetranscription in the splenocytes. Remarkably, a robust polyfunctional T cell response,with inhibition of Th2 profile, is characterized by an increase in the expression of il-6,il-10, il-12, tnf-a, ifn-g and tgf-b genes. These findings suggest that hydatid fluidinduced autophagy in dendritic cells plays a crucial role in shaping the subsequent Tcell responses, which is important for a better understanding of host-parasiteinteractions in cystic echinococcosis.