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CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion
Lethal fungal sepsis causes high morbidity and mortality in intensive care patients. Fungal infections have an immunological basis, and it has been shown in recent studies that decreased CD8(+) T-cell count in fungal infections is related to prognosis, while the underlying mechanism is still unclear...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241777/ https://www.ncbi.nlm.nih.gov/pubmed/34220329 http://dx.doi.org/10.7150/ijms.55592 |
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author | Wang, Hao Han, Wen Guo, Ran Bai, Guangxu Chen, Jianwei Cui, Na |
author_facet | Wang, Hao Han, Wen Guo, Ran Bai, Guangxu Chen, Jianwei Cui, Na |
author_sort | Wang, Hao |
collection | PubMed |
description | Lethal fungal sepsis causes high morbidity and mortality in intensive care patients. Fungal infections have an immunological basis, and it has been shown in recent studies that decreased CD8(+) T-cell count in fungal infections is related to prognosis, while the underlying mechanism is still unclear. Here, a lethal fungal sepsis model induced by candidemia was created and we found a decreased CD8(+) T-cell count and exaggerated apoptosis. Simultaneously, expression of light chain (LC)3B in CD8(+) T cells increased, along with increased autophagosomes and accumulation of p62 in infected mice. We regulated the activity of the mammalian target of rapamycin (mTOR) pathway using T-cell-specific mTOR/ TSC1 deletion mice. We observed increased number of autophagosomes and expression of LC3B in CD8(+)T cells after T-cell-specific mTOR knockout, while accumulation of p62 was not ameliorated, and there was no increase in the number of autolysosomes. Apoptosis rate and expression of BIM, a pro-apoptotic gene, decreased in CD8(+) T cells in mTOR-deletion mice but increased in TSC1-deletion mice. Our results showed increased CD8(+) T-cell death in spleen of lethal fungal sepsis mice, and decreased expression of mTOR ameliorated CD8(+) T-cell survival. mTOR may be a possible target to reverse CD8(+) T-cell immune dysfunction in lethal fungal sepsis. |
format | Online Article Text |
id | pubmed-8241777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-82417772021-07-01 CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion Wang, Hao Han, Wen Guo, Ran Bai, Guangxu Chen, Jianwei Cui, Na Int J Med Sci Research Paper Lethal fungal sepsis causes high morbidity and mortality in intensive care patients. Fungal infections have an immunological basis, and it has been shown in recent studies that decreased CD8(+) T-cell count in fungal infections is related to prognosis, while the underlying mechanism is still unclear. Here, a lethal fungal sepsis model induced by candidemia was created and we found a decreased CD8(+) T-cell count and exaggerated apoptosis. Simultaneously, expression of light chain (LC)3B in CD8(+) T cells increased, along with increased autophagosomes and accumulation of p62 in infected mice. We regulated the activity of the mammalian target of rapamycin (mTOR) pathway using T-cell-specific mTOR/ TSC1 deletion mice. We observed increased number of autophagosomes and expression of LC3B in CD8(+)T cells after T-cell-specific mTOR knockout, while accumulation of p62 was not ameliorated, and there was no increase in the number of autolysosomes. Apoptosis rate and expression of BIM, a pro-apoptotic gene, decreased in CD8(+) T cells in mTOR-deletion mice but increased in TSC1-deletion mice. Our results showed increased CD8(+) T-cell death in spleen of lethal fungal sepsis mice, and decreased expression of mTOR ameliorated CD8(+) T-cell survival. mTOR may be a possible target to reverse CD8(+) T-cell immune dysfunction in lethal fungal sepsis. Ivyspring International Publisher 2021-06-16 /pmc/articles/PMC8241777/ /pubmed/34220329 http://dx.doi.org/10.7150/ijms.55592 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wang, Hao Han, Wen Guo, Ran Bai, Guangxu Chen, Jianwei Cui, Na CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion |
title | CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion |
title_full | CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion |
title_fullStr | CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion |
title_full_unstemmed | CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion |
title_short | CD8(+) T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion |
title_sort | cd8(+) t cell survival in lethal fungal sepsis was ameliorated by t-cell-specific mtor deletion |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241777/ https://www.ncbi.nlm.nih.gov/pubmed/34220329 http://dx.doi.org/10.7150/ijms.55592 |
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