Glycomolecules in Echinococcus granulosus cyst fluid inhibit TLR4-mediated inflammatory responses via c-Raf

Hou, Jun; Li, Linlin; Dong, Di; Wang, Lianghai; Wang, Xian; Yang, Kun; Xu, Xiaodan; Chen, Congzhe; Wu, Xiangwei; Chen, Xueling

doi:10.1038/s41423-019-0314-1

Cited by 10 publications

(12 citation statements)

References 10 publications

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“…We have previously reported that exosome-like vesicles induce maturation of BMDCs with an increase of CD86 and a slight down-regulation in the expression of MHC II molecule 57 . Likewise, previous reports have shown a weak maturation phenotype in mouse and human DCs upon stimulation with Eg antigens in combination with potent immunogens 35 , 37 , 58 – 62 . Uptake and processing of antigens by immature DCs are critical steps in producing an immune response.…”

Section: Discussionsupporting

confidence: 60%

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

Rodrígues

Nicolao

Chop

et al. 2021

Sci Rep

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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.

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Section: Discussionsupporting

confidence: 60%

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

Rodrígues

Nicolao

Chop

et al. 2021

Sci Rep

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show abstract

“…We have previously reported that exosome-like vesicles induce maturation of BMDCs with an increase of CD86 and a slight downregulation in the expression of MHC II molecule 56 . Likewise, previous reports have shown a weak maturation phenotype in mouse and human DCs upon stimulation with Eg antigens in combination with potent immunogens 36,38,57,[57][58][59][60][61] . Uptake and processing of antigens by immature DCs are critical steps in producing an immune response.…”

Section: Discussionmentioning

confidence: 56%

“…In all conditions tested, rapamycin diminished gene transcription. HF and particularly Antigen B reduced the production of IL-12p70 and TNF- in LPS-stimulated DCs 60,61 . The same expression pattern was observed when DCs were exposed with HF during differentiation.…”

Section: Discussionmentioning

confidence: 97%

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

Rodrígues

Nicolao

Chop

et al. 2020

Preprint

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1.AbstractImmune 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.

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“…Cells were resuspended and plated in six-well plates at a density of 1 × 10 6 cells per well in DMEM containing L-glutamine supplemented with 10% fetal bovine serum (FBS) according to previous reports (Chen et al, 2020;Gao et al, 2020;He et al, 2020). After overnight culture, the non-adherent cells were removed, and the attached cells (enriched in peritoneal macrophages) were treated with LPS (1 μg mL −1 ) or LPS and EgCF (2.15 mg mL −1 ) for the indicated periods as a previous report (Hou et al, 2020).…”

Section: Cells and Cell Culturementioning

confidence: 99%

“…Besides protoscoleces, various immunomodulatory effects have been attributed to EgCF (Mokhtari Amirmajdi et al, 2011; Wang et al, 2015a;Zhou et al, 2019;Yang et al, 2021). We have previously demonstrated glycomolecules in EgCF could interfere with the Toll-like receptor 4 (TLR4)-mediated activation of DCs and the downstream inflammatory factors (Hou et al, 2020). Additionally, EgCF could promote T lymphocytes' differentiation into Treg cells and induce transforming growth factor-β secretion, subsequently impairing NK cell effector function (Yin et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Echinococcus granulosus cyst fluid suppresses inflammatory responses by inhibiting TRAF6 signalling in macrophages

Lin

Zhou

et al. 2021

Parasitology

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Glycomolecules in Echinococcus granulosus cyst fluid inhibit TLR4-mediated inflammatory responses via c-Raf

Cited by 10 publications

References 10 publications

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

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

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

Echinococcus granulosus cyst fluid suppresses inflammatory responses by inhibiting TRAF6 signalling in macrophages

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