Impact of mTOR signaling pathway on CD8+ T cell immunity through Eomesodermin in response to invasive candidiasis

Abstract

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).

Keywords

• CD8+ T cells
• Eomesodermin
• Invasive candidiasis
• Mammalian target of rapamycin