Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2.
Background Clonorchis sinensis, a fluke dwelling in the intrahepatic bile ducts causes clonorchiasis, which affect about 15 million people wide-distributed in eastern Asia. During C. sinensis infection, worm-host interaction results in activation of patterns recognition receptors (PRRs) such as Toll...
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ftdoajarticles:oai:doaj.org/article:918acaefd7e347e28acc624b218dc4b5 2023-05-15T15:12:39+02:00 Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2. Chao Yan Fan Fang Yu-Zhao Zhang Xin Dong Jing Wu Hai-Liang Liu Chun-Yang Fan Stephane Koda Bei-Bei Zhang Qian Yu Liang Wang Yu-Gang Wang Jia-Xu Chen Kui-Yang Zheng 2020-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008643 https://doaj.org/article/918acaefd7e347e28acc624b218dc4b5 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008643 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008643 https://doaj.org/article/918acaefd7e347e28acc624b218dc4b5 PLoS Neglected Tropical Diseases, Vol 14, Iss 10, p e0008643 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008643 2022-12-31T05:59:57Z Background Clonorchis sinensis, a fluke dwelling in the intrahepatic bile ducts causes clonorchiasis, which affect about 15 million people wide-distributed in eastern Asia. During C. sinensis infection, worm-host interaction results in activation of patterns recognition receptors (PRRs) such as Toll-like receptors (TLRs) and further triggers immune responses, which determines the outcome of the infection. However, the mechanisms by which pathogen-associated molecules patterns from C. sinensis interact with TLRs were poorly understood. In the present study, we assumed that the molecules from C. sinensis may regulate host immune responses via TLR2 signaling pathway. Methodology/principal findings In the present study, we have identified a ~34 kDa CsHscB from C. sinensis which physically bound with TLR2 as demonstrated by molecular docking and pull-down assay. We also found that recombinant CsHscB (rCsHscB) potently activates macrophage to express various proteins including TLR2, CD80, MHCII, and cytokines like IL-6, TNF-α, and IL-10, but rCsHscB failed to induce IL-10 in macrophages from Tlr2-/- mice. Moreover, ERK1/2 activation was required for rCsHscB-induced IL-10 production in macrophages. In vivo study revealed that rCsHscB triggered a high production of IL-10 in the wild-type (WT) but not in Tlr2-/- mice. Consistently, the phosphorylation of ERK1/2 was also attenuated in Tlr2-/- mice compared to the WT mice, after the treatment with rCsHscB. Conclusions/significance Our data thus demonstrate that rCsHscB from C. sinensis interacts with TLR2 to be endowed with immune regulatory activities, and may have some therapeutic implications in future beyond parasitology. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 10 e0008643 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Chao Yan Fan Fang Yu-Zhao Zhang Xin Dong Jing Wu Hai-Liang Liu Chun-Yang Fan Stephane Koda Bei-Bei Zhang Qian Yu Liang Wang Yu-Gang Wang Jia-Xu Chen Kui-Yang Zheng Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Clonorchis sinensis, a fluke dwelling in the intrahepatic bile ducts causes clonorchiasis, which affect about 15 million people wide-distributed in eastern Asia. During C. sinensis infection, worm-host interaction results in activation of patterns recognition receptors (PRRs) such as Toll-like receptors (TLRs) and further triggers immune responses, which determines the outcome of the infection. However, the mechanisms by which pathogen-associated molecules patterns from C. sinensis interact with TLRs were poorly understood. In the present study, we assumed that the molecules from C. sinensis may regulate host immune responses via TLR2 signaling pathway. Methodology/principal findings In the present study, we have identified a ~34 kDa CsHscB from C. sinensis which physically bound with TLR2 as demonstrated by molecular docking and pull-down assay. We also found that recombinant CsHscB (rCsHscB) potently activates macrophage to express various proteins including TLR2, CD80, MHCII, and cytokines like IL-6, TNF-α, and IL-10, but rCsHscB failed to induce IL-10 in macrophages from Tlr2-/- mice. Moreover, ERK1/2 activation was required for rCsHscB-induced IL-10 production in macrophages. In vivo study revealed that rCsHscB triggered a high production of IL-10 in the wild-type (WT) but not in Tlr2-/- mice. Consistently, the phosphorylation of ERK1/2 was also attenuated in Tlr2-/- mice compared to the WT mice, after the treatment with rCsHscB. Conclusions/significance Our data thus demonstrate that rCsHscB from C. sinensis interacts with TLR2 to be endowed with immune regulatory activities, and may have some therapeutic implications in future beyond parasitology. |
format |
Article in Journal/Newspaper |
author |
Chao Yan Fan Fang Yu-Zhao Zhang Xin Dong Jing Wu Hai-Liang Liu Chun-Yang Fan Stephane Koda Bei-Bei Zhang Qian Yu Liang Wang Yu-Gang Wang Jia-Xu Chen Kui-Yang Zheng |
author_facet |
Chao Yan Fan Fang Yu-Zhao Zhang Xin Dong Jing Wu Hai-Liang Liu Chun-Yang Fan Stephane Koda Bei-Bei Zhang Qian Yu Liang Wang Yu-Gang Wang Jia-Xu Chen Kui-Yang Zheng |
author_sort |
Chao Yan |
title |
Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2. |
title_short |
Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2. |
title_full |
Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2. |
title_fullStr |
Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2. |
title_full_unstemmed |
Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2. |
title_sort |
recombinant cshscb of carcinogenic liver fluke clonorchis sinensis induces il-10 production by binding with tlr2. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008643 https://doaj.org/article/918acaefd7e347e28acc624b218dc4b5 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 10, p e0008643 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008643 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008643 https://doaj.org/article/918acaefd7e347e28acc624b218dc4b5 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008643 |
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PLOS Neglected Tropical Diseases |
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14 |
container_issue |
10 |
container_start_page |
e0008643 |
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