Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

CHRISTIAN RODRIGUEZ RODRIGUES; MARÍA CELESTE NICOLAO; MAIA CHOP; NATALIA PLÁ; MORA MASSARO; JULIA LOOS; ANDREA C. CUMINO

Scientific Reports

Springer Nature

Lugar: Londres; Año: 2021

Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innateimmune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosusby dendritic cells (DCs) is a key determinant of the host?s response to this parasite. Given that mTORsignaling pathway has been described as a regulator linking metabolism and immune function in DCs,we reported for the first time in these cells, global translation levels, antigen uptake, phenotype,cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid(HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulationof CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HFdid not increase the expression of any co-stimulatory molecules, but also down-modulated CD40and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigenspromoted protein synthesis through mTOR activation. The use of rapamycin decreased the expressionof the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyteproliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positivestructures in DCs which play critical roles in the presentation of these antigens to T cells