Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi · 2021
Impact of mTOR signaling pathway on CD8+ T cell immunity through Eomesodermin in response to invasive candidiasis.
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Zhang Jiahui, Cui Na, Wang Hao, Han Wen, Bai Guangxu, Cheng Wei
Аннотация
BACKGROUND: We investigated the effect of the mammalian target of rapamycin (mTOR) pathway on CD8+ T cell immunity through Eomesodermin (Eomes) in intensive care unit (ICU) patients with invasive candidiasis (IC) and in a mouse model.
METHODS: We evaluated quantitative changes in parameters of the mTOR/phosphorylated ribosomal S6 kinase (pS6K) pathway and immune system at the onset of infection in ICU patients. The study was registered on 28 February 2017 at chictr.org.cn (ChiCTR-ROC-17010750). We also used a mouse model of Candida infection and constructed T-cell-specific mTOR and T-cell-specific tuberous sclerosis complex (TSC) 1 conditional knockout mice to elucidate the molecular mechanisms.
RESULTS: We enrolled 88 patients, including 8 with IC. The IC group had lower CD8+ T cell counts, higher serum levels of mTOR, pS6K, Eomes and interleukin (IL)-6. The mouse model with IC showed results consistent in the clinical study. The CD8+ T cell immune response to IC seemed to be weakened in TSC1 knockout mice compared with wild-type IC mice, demonstrating that mTOR activation resulted in the impaired CD8+ T cell immunity in IC.
CONCLUSIONS: In IC, the mTOR activation may play a vital role in impaired CD8+ T cell immunity through enhancing expression of Eomes. The study was registered on 28 February 2017 at chictr.org.cn (identifier ChiCTR-ROC-17010750).
METHODS: We evaluated quantitative changes in parameters of the mTOR/phosphorylated ribosomal S6 kinase (pS6K) pathway and immune system at the onset of infection in ICU patients. The study was registered on 28 February 2017 at chictr.org.cn (ChiCTR-ROC-17010750). We also used a mouse model of Candida infection and constructed T-cell-specific mTOR and T-cell-specific tuberous sclerosis complex (TSC) 1 conditional knockout mice to elucidate the molecular mechanisms.
RESULTS: We enrolled 88 patients, including 8 with IC. The IC group had lower CD8+ T cell counts, higher serum levels of mTOR, pS6K, Eomes and interleukin (IL)-6. The mouse model with IC showed results consistent in the clinical study. The CD8+ T cell immune response to IC seemed to be weakened in TSC1 knockout mice compared with wild-type IC mice, demonstrating that mTOR activation resulted in the impaired CD8+ T cell immunity in IC.
CONCLUSIONS: In IC, the mTOR activation may play a vital role in impaired CD8+ T cell immunity through enhancing expression of Eomes. The study was registered on 28 February 2017 at chictr.org.cn (identifier ChiCTR-ROC-17010750).