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The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development

TLRs (Toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. Although several TLRs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of TLRs in the development of t...

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Autores principales: Zheng, Hong, Tan, Zhangping, Zhou, TaoLi, Zhu, Feng, Ding, Yan, Liu, Taiping, Wu, Yuzhang, Xu, Wenyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678895/
https://www.ncbi.nlm.nih.gov/pubmed/26667391
http://dx.doi.org/10.1038/srep18239
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author Zheng, Hong
Tan, Zhangping
Zhou, TaoLi
Zhu, Feng
Ding, Yan
Liu, Taiping
Wu, Yuzhang
Xu, Wenyue
author_facet Zheng, Hong
Tan, Zhangping
Zhou, TaoLi
Zhu, Feng
Ding, Yan
Liu, Taiping
Wu, Yuzhang
Xu, Wenyue
author_sort Zheng, Hong
collection PubMed
description TLRs (Toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. Although several TLRs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of TLRs in the development of the pre-erythrocytic stage is still largely unknown. Here, we found that sporozoite and its lysate could significantly activate the TLR2, and induce macrophages to release proinflammatory cytokines, including IL-6, MCP-1 and TNF-α, in a TLR2-dependent manner. Further studies showed that sporozoite and its lysate could be recognized by either TLR2 homodimers or TLR2/1 and TLR2/6 heterodimers, implicating the complexity of TLR2 agonist in sporozoite. Interestingly, the TLR2 signaling can significantly suppress the development of the pre-erythrocytic stage of Plasmodium yoelii, as both liver parasite load and subsequent parasitemia were significantly elevated in both TLR2- and MyD88-deficient mice. Additionally, the observed higher level of parasite burden in TLR2(−/−) mice was found to be closely associated with a reduction in proinflammatory cytokines in the liver. Therefore, we provide the first evidence that sporozoites can activate the TLR2 signaling, which in turn significantly inhibits the intrahepatic parasites. This may provide us with novel clues to design preventive anti-malaria therapies.
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spelling pubmed-46788952015-12-18 The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development Zheng, Hong Tan, Zhangping Zhou, TaoLi Zhu, Feng Ding, Yan Liu, Taiping Wu, Yuzhang Xu, Wenyue Sci Rep Article TLRs (Toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. Although several TLRs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of TLRs in the development of the pre-erythrocytic stage is still largely unknown. Here, we found that sporozoite and its lysate could significantly activate the TLR2, and induce macrophages to release proinflammatory cytokines, including IL-6, MCP-1 and TNF-α, in a TLR2-dependent manner. Further studies showed that sporozoite and its lysate could be recognized by either TLR2 homodimers or TLR2/1 and TLR2/6 heterodimers, implicating the complexity of TLR2 agonist in sporozoite. Interestingly, the TLR2 signaling can significantly suppress the development of the pre-erythrocytic stage of Plasmodium yoelii, as both liver parasite load and subsequent parasitemia were significantly elevated in both TLR2- and MyD88-deficient mice. Additionally, the observed higher level of parasite burden in TLR2(−/−) mice was found to be closely associated with a reduction in proinflammatory cytokines in the liver. Therefore, we provide the first evidence that sporozoites can activate the TLR2 signaling, which in turn significantly inhibits the intrahepatic parasites. This may provide us with novel clues to design preventive anti-malaria therapies. Nature Publishing Group 2015-12-15 /pmc/articles/PMC4678895/ /pubmed/26667391 http://dx.doi.org/10.1038/srep18239 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zheng, Hong
Tan, Zhangping
Zhou, TaoLi
Zhu, Feng
Ding, Yan
Liu, Taiping
Wu, Yuzhang
Xu, Wenyue
The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development
title The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development
title_full The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development
title_fullStr The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development
title_full_unstemmed The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development
title_short The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development
title_sort tlr2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678895/
https://www.ncbi.nlm.nih.gov/pubmed/26667391
http://dx.doi.org/10.1038/srep18239
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