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Loss of natural resistance to schistosome in T cell deficient rat

Schistosomiasis is among the major neglected tropical diseases and effective prevention by boosting the immune system is still not available. T cells are key cellular components governing adaptive immune response to various infections. While common laboratory mice, such as C57BL/6, are highly suscep...

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Autores principales: Lu, Liaoxun, Hu, Junjian, Chao, Tianzhu, Chen, Zhijun, Liu, Zhuangzhuang, Luo, Xinsong, Liang, Yinming, He, Pei, Zhang, Lichen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785244/
https://www.ncbi.nlm.nih.gov/pubmed/33347431
http://dx.doi.org/10.1371/journal.pntd.0008909
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author Lu, Liaoxun
Hu, Junjian
Chao, Tianzhu
Chen, Zhijun
Liu, Zhuangzhuang
Luo, Xinsong
Liang, Yinming
He, Pei
Zhang, Lichen
author_facet Lu, Liaoxun
Hu, Junjian
Chao, Tianzhu
Chen, Zhijun
Liu, Zhuangzhuang
Luo, Xinsong
Liang, Yinming
He, Pei
Zhang, Lichen
author_sort Lu, Liaoxun
collection PubMed
description Schistosomiasis is among the major neglected tropical diseases and effective prevention by boosting the immune system is still not available. T cells are key cellular components governing adaptive immune response to various infections. While common laboratory mice, such as C57BL/6, are highly susceptible to schistosomiasis, the SD rats are extremely resistant. However, whether adaptive immunity is necessary for such natural resistance to schistosomiasis in rats remains to be determined. Therefore, it is necessary to establish genetic model deficient in T cells and adaptive immunity on the resistant SD background, and to characterize liver pathology during schistosomiasis. In this study we compared experimental schistosomiasis in highly susceptible C57BL/6 (B6) mice and in resistant SD rats, using cercariae of Schistosoma japonicum. We observed a marked T cell expansion in the spleen of infected B6 mice, but not resistant SD rats. Interestingly, CD3e(−/−) B6 mice in which T cells are completely absent, the infectious burden of adult worms was significantly higher than that in WT mice, suggesting an anti-parasitic role for T cells in B6 mice during schistosome infection. In further experiments, we established Lck deficient SD rats by using CRISPR/Cas9 in which T cell development was completely abolished. Strikingly, we found that such Lck deficiency in SD rats severely impaired their natural resistance to schistosome infection, and fostered parasite growth. Together with an additional genetic model deficient in T cells, the CD3e(−/−) SD rats, we confirmed the absence of T cell resulted in loss of natural resistance to schistosome infection, but also mitigated liver immunopathology. Our further experiments showed that regulatory T cell differentiation in infected SD rats was significantly decreased during schistosomiasis, in contrast to significant increase of regulatory T cells in infected B6 mice. These data suggest that T cell mediated immune tolerance facilitates persistent infection in mice but not in SD rats. The demonstration of an important role for T cells in natural resistance of SD rats to schistosomiasis provides experimental evidences supporting the rationale to boost T cell responses in humans to prevent and treat schistosomiasis.
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spelling pubmed-77852442021-01-13 Loss of natural resistance to schistosome in T cell deficient rat Lu, Liaoxun Hu, Junjian Chao, Tianzhu Chen, Zhijun Liu, Zhuangzhuang Luo, Xinsong Liang, Yinming He, Pei Zhang, Lichen PLoS Negl Trop Dis Research Article Schistosomiasis is among the major neglected tropical diseases and effective prevention by boosting the immune system is still not available. T cells are key cellular components governing adaptive immune response to various infections. While common laboratory mice, such as C57BL/6, are highly susceptible to schistosomiasis, the SD rats are extremely resistant. However, whether adaptive immunity is necessary for such natural resistance to schistosomiasis in rats remains to be determined. Therefore, it is necessary to establish genetic model deficient in T cells and adaptive immunity on the resistant SD background, and to characterize liver pathology during schistosomiasis. In this study we compared experimental schistosomiasis in highly susceptible C57BL/6 (B6) mice and in resistant SD rats, using cercariae of Schistosoma japonicum. We observed a marked T cell expansion in the spleen of infected B6 mice, but not resistant SD rats. Interestingly, CD3e(−/−) B6 mice in which T cells are completely absent, the infectious burden of adult worms was significantly higher than that in WT mice, suggesting an anti-parasitic role for T cells in B6 mice during schistosome infection. In further experiments, we established Lck deficient SD rats by using CRISPR/Cas9 in which T cell development was completely abolished. Strikingly, we found that such Lck deficiency in SD rats severely impaired their natural resistance to schistosome infection, and fostered parasite growth. Together with an additional genetic model deficient in T cells, the CD3e(−/−) SD rats, we confirmed the absence of T cell resulted in loss of natural resistance to schistosome infection, but also mitigated liver immunopathology. Our further experiments showed that regulatory T cell differentiation in infected SD rats was significantly decreased during schistosomiasis, in contrast to significant increase of regulatory T cells in infected B6 mice. These data suggest that T cell mediated immune tolerance facilitates persistent infection in mice but not in SD rats. The demonstration of an important role for T cells in natural resistance of SD rats to schistosomiasis provides experimental evidences supporting the rationale to boost T cell responses in humans to prevent and treat schistosomiasis. Public Library of Science 2020-12-21 /pmc/articles/PMC7785244/ /pubmed/33347431 http://dx.doi.org/10.1371/journal.pntd.0008909 Text en © 2020 Lu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lu, Liaoxun
Hu, Junjian
Chao, Tianzhu
Chen, Zhijun
Liu, Zhuangzhuang
Luo, Xinsong
Liang, Yinming
He, Pei
Zhang, Lichen
Loss of natural resistance to schistosome in T cell deficient rat
title Loss of natural resistance to schistosome in T cell deficient rat
title_full Loss of natural resistance to schistosome in T cell deficient rat
title_fullStr Loss of natural resistance to schistosome in T cell deficient rat
title_full_unstemmed Loss of natural resistance to schistosome in T cell deficient rat
title_short Loss of natural resistance to schistosome in T cell deficient rat
title_sort loss of natural resistance to schistosome in t cell deficient rat
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785244/
https://www.ncbi.nlm.nih.gov/pubmed/33347431
http://dx.doi.org/10.1371/journal.pntd.0008909
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