4.5 Article

CD8+ T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion

期刊

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
卷 18, 期 13, 页码 3004-3013

出版社

IVYSPRING INT PUBL
DOI: 10.7150/ijms.55592

关键词

lethal fungal sepsis; CD8(+)T cell survival; mammalian target of rapamycin (mTOR); autophagy

资金

  1. Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019XK320040]
  2. National Natural Science Foundation of China [81601657]
  3. Tibet Natural Science Foundation [XZ2019ZR-ZY12(Z)]
  4. Wu Jieping Medical Foundation [320.6750.18419]
  5. Excellence Program of Key Clinical Specialty of Beijing in 2020 [ZK128001]

向作者/读者索取更多资源

Fungal infections lead to decreased CD8+ T-cell count and exaggerated apoptosis, with mTOR potentially being a key target to improve CD8+ T-cell immune function.
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.

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