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

Abstract Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host's response to this parasite....

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Autores principales: Christian Rodriguez Rodrigues, María Celeste Nicolao, Maia Chop, Natalia Plá, Mora Massaro, Julia Loos, Andrea C. Cumino
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:1585f728a2d14505ac27015521338fca2021-12-02T19:02:35ZModulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition10.1038/s41598-021-96435-z2045-2322https://doaj.org/article/1585f728a2d14505ac27015521338fca2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96435-zhttps://doaj.org/toc/2045-2322Abstract Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host's response to this parasite. Given that mTOR signaling 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-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.Christian Rodriguez RodriguesMaría Celeste NicolaoMaia ChopNatalia PláMora MassaroJulia LoosAndrea C. CuminoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Christian Rodriguez Rodrigues
María Celeste Nicolao
Maia Chop
Natalia Plá
Mora Massaro
Julia Loos
Andrea C. Cumino
Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
description Abstract Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host's response to this parasite. Given that mTOR signaling 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-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.
format article
author Christian Rodriguez Rodrigues
María Celeste Nicolao
Maia Chop
Natalia Plá
Mora Massaro
Julia Loos
Andrea C. Cumino
author_facet Christian Rodriguez Rodrigues
María Celeste Nicolao
Maia Chop
Natalia Plá
Mora Massaro
Julia Loos
Andrea C. Cumino
author_sort Christian Rodriguez Rodrigues
title Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_short Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_full Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_fullStr Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_full_unstemmed Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_sort modulation of the mtor pathway plays a central role in dendritic cell functions after echinococcus granulosus antigen recognition
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/1585f728a2d14505ac27015521338fca
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