CD8+ T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion |
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Authors: | Hao Wang Wen Han Ran Guo Guangxu Bai Jianwei Chen Na Cui |
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Affiliation: | 1.Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China.;2.Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science; Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing 100730, China. |
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Abstract: | 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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Keywords: | lethal fungal sepsis CD8+T cell survival mammalian target of rapamycin (mTOR) autophagy |
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