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mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis
CD8(+) T cells are a vital component of the adaptive immune system and important for eliminating intracellular pathogens. Notably, mTOR activity is associated with CD8(+) T effector memory (Tem) cell differentiation in fungal infections. This study investigates the molecular mechanisms of CD8(+) Tem...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
De Gruyter
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874697/ https://www.ncbi.nlm.nih.gov/pubmed/33817078 http://dx.doi.org/10.1515/biol-2018-0018 |
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author | Wang, Hao Xiao, Yu Su, Longxiang Cui, Na Liu, Dawei |
author_facet | Wang, Hao Xiao, Yu Su, Longxiang Cui, Na Liu, Dawei |
author_sort | Wang, Hao |
collection | PubMed |
description | CD8(+) T cells are a vital component of the adaptive immune system and important for eliminating intracellular pathogens. Notably, mTOR activity is associated with CD8(+) T effector memory (Tem) cell differentiation in fungal infections. This study investigates the molecular mechanisms of CD8(+) Tem cell proliferation and differentiation mediated by the mTOR pathway in immunosuppressed mice with invasive pulmonary aspergillosis (IPA). We first established the immunosuppressed IPA mouse model, then mice were subjected to rapamycin treatment daily or interleukin (IL)-12 treatment every other day. Lung tissues and blood samples were obtained seven days later. Aspergillus fumigatus was cultured from the lung tissue of mice inoculated with A. fumigatus spores. After IL-12 treatment, the expression of mTOR and its downstream signaling molecule S6 kinase, number of CD8(+) Tem cells and interferon-γ expression were significantly increased, while they were significantly decreased after treatment with rapamycin. Additionally, IL-12 treatment induced T-bet but inhibited Eomesodermin expression, while the opposite was seen when the mTOR pathway was blocked by rapamycin. In conclusion, we found that the mTOR pathway induced CD8(+) T cell proliferation and differentiation by regulating T-bet and Eomesodermin expression, which significantly influenced immune regulation during IPA and enhanced the immune response against fungal infection. |
format | Online Article Text |
id | pubmed-7874697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | De Gruyter |
record_format | MEDLINE/PubMed |
spelling | pubmed-78746972021-04-01 mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis Wang, Hao Xiao, Yu Su, Longxiang Cui, Na Liu, Dawei Open Life Sci Research Article CD8(+) T cells are a vital component of the adaptive immune system and important for eliminating intracellular pathogens. Notably, mTOR activity is associated with CD8(+) T effector memory (Tem) cell differentiation in fungal infections. This study investigates the molecular mechanisms of CD8(+) Tem cell proliferation and differentiation mediated by the mTOR pathway in immunosuppressed mice with invasive pulmonary aspergillosis (IPA). We first established the immunosuppressed IPA mouse model, then mice were subjected to rapamycin treatment daily or interleukin (IL)-12 treatment every other day. Lung tissues and blood samples were obtained seven days later. Aspergillus fumigatus was cultured from the lung tissue of mice inoculated with A. fumigatus spores. After IL-12 treatment, the expression of mTOR and its downstream signaling molecule S6 kinase, number of CD8(+) Tem cells and interferon-γ expression were significantly increased, while they were significantly decreased after treatment with rapamycin. Additionally, IL-12 treatment induced T-bet but inhibited Eomesodermin expression, while the opposite was seen when the mTOR pathway was blocked by rapamycin. In conclusion, we found that the mTOR pathway induced CD8(+) T cell proliferation and differentiation by regulating T-bet and Eomesodermin expression, which significantly influenced immune regulation during IPA and enhanced the immune response against fungal infection. De Gruyter 2018-05-04 /pmc/articles/PMC7874697/ /pubmed/33817078 http://dx.doi.org/10.1515/biol-2018-0018 Text en © 2018 Hao Wang et al., published by De Gruyter http://creativecommons.org/licenses/by-nc-nd/4.0 This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. |
spellingShingle | Research Article Wang, Hao Xiao, Yu Su, Longxiang Cui, Na Liu, Dawei mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis |
title | mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis |
title_full | mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis |
title_fullStr | mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis |
title_full_unstemmed | mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis |
title_short | mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis |
title_sort | mtor modulates cd8+ t cell differentiation in mice with invasive pulmonary aspergillosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874697/ https://www.ncbi.nlm.nih.gov/pubmed/33817078 http://dx.doi.org/10.1515/biol-2018-0018 |
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