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 A; CUMINO ANDREA C; RODRIGEZ R. CHRISTIAN

Front. Cell. Infect. Microbiol.

Frontiers

Año: 2024 vol. 14

2235-2988

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 the underlyingmolecular mechanisms involved in hydatid fluid-induced autophagy, we analyzed theexpression of autophagy-related genes in stimulated dendritic cells. Our resultsdemonstrated a significant upregulation of beclin-1, atg16l1 and atg12, indicating theinduction of autophagy machinery in response to hydatid fluid exposure.Additionally, using confocal microscopy, we observed an accumulation of LC3 indendritic cell autophagosomes, confirming the activation of this catabolic pathwayassociated with antigen presentation. Finally, to evaluate the functional consequencesof hydatid fluid-induced autophagy in DCs, we evaluated cytokine transcription in thesplenocytes. Remarkably, a robust polyfunctional T cell response, with inhibition ofTh2 profile, is characterized by an increase in the expression of il-6, il-10, il-12, tnfIn review3ifn-g and tgf-b genes T ese findings suggest that hydatid fluid-induced autophagyin dendritic cells plays a crucial role in shaping the subsequent T cell responses,which is important for a better understanding of host-parasite interactions in cysticechinococcosis.