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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ftdoajarticles:oai:doaj.org/article:d70c1caa6ef54a4eb3d10cc1aed77f47 2023-05-15T15:15:28+02:00 Loss of natural resistance to schistosome in T cell deficient rat. Liaoxun Lu Junjian Hu Tianzhu Chao Zhijun Chen Zhuangzhuang Liu Xinsong Luo Yinming Liang Pei He Lichen Zhang 2020-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008909 https://doaj.org/article/d70c1caa6ef54a4eb3d10cc1aed77f47 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008909 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008909 https://doaj.org/article/d70c1caa6ef54a4eb3d10cc1aed77f47 PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0008909 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008909 2022-12-31T07:46:16Z 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 ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 12 e0008909 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Liaoxun Lu Junjian Hu Tianzhu Chao Zhijun Chen Zhuangzhuang Liu Xinsong Luo Yinming Liang Pei He Lichen Zhang Loss of natural resistance to schistosome in T cell deficient rat. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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 ... |
format |
Article in Journal/Newspaper |
author |
Liaoxun Lu Junjian Hu Tianzhu Chao Zhijun Chen Zhuangzhuang Liu Xinsong Luo Yinming Liang Pei He Lichen Zhang |
author_facet |
Liaoxun Lu Junjian Hu Tianzhu Chao Zhijun Chen Zhuangzhuang Liu Xinsong Luo Yinming Liang Pei He Lichen Zhang |
author_sort |
Liaoxun Lu |
title |
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_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_sort |
loss of natural resistance to schistosome in t cell deficient rat. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008909 https://doaj.org/article/d70c1caa6ef54a4eb3d10cc1aed77f47 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0008909 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008909 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008909 https://doaj.org/article/d70c1caa6ef54a4eb3d10cc1aed77f47 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008909 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
12 |
container_start_page |
e0008909 |
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1766345845020557312 |