Sepsis-associated encephalopathy (SAE) increases not only morbidity and mortality but has been associated with long-lasting mental impairment after hospital discharge in septic patients. Recently, studies have shown that these mental impairments are caused by infection-induced neuroinflammation. However, the role of T cells in the pathogenesis of SAE and mental impairments remains unclear. Thus, in this study, we aimed to clarify how immune cells, especially T cells, influence the development and recovery of these disorders. In the cecal slurry (CS)-induced septic mouse model, we performed three different kinds of behavioral tests, open-field test, marble burying test, and forced swimming test, and observed anxiety-like behavior in septic mice. Additionally, increased interleukin (IL)-1β and IL-6 expression levels, and infiltration of neutrophils and T cells were examined in the brain of septic mice, 10 days after sepsis onset. Twenty days after sepsis onset, the septic mice could recover the number of astrocytes. At day 30, expression levels of IL-1β and tumor necrosis factor (TNF)-α returned to normal levels in the cerebral cortex of septic mice. Interestingly, resolution of neuroinflammation and alleviation of depression were delayed in septic mice treated with FTY720, which inhibits sphingosine-1-phosphate (S1P)-dependent lymphocyte egress from lymph nodes. On analyzing the brain T cells with or without FTY720 in septic mice, the FTY720 untreated mice presented increased regulatory T cells (Treg) and Th2 cells in the brain, whereas the FTY720 treated mice demonstrated increased Th17 in the brain at day 30. Furthermore, in FTY720 treated septic mice, the number of astrocytes in the cerebral cortex remained reduced at day 30. These results suggest that infiltrated Treg and Th2 cells contribute to the attenuation SAE and alleviate SAE-induce mental disorder by resolving neuroinflammation in the chronic phase of sepsis.

中文翻译：

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大脑中浸润的调节性 T 细胞和 Th2 细胞有助于减轻脓毒症相关脑病和减轻患有多种微生物脓毒症的小鼠的精神障碍

脓毒症相关脑病 (SAE) 不仅会增加发病率和死亡率，而且与脓毒症患者出院后的长期精神障碍有关。最近，研究表明，这些精神障碍是由感染引起的神经炎症引起的。然而，T 细胞在 SAE 和精神障碍发病机制中的作用仍不清楚。因此，在本研究中，我们旨在阐明免疫细胞，尤其是 T 细胞如何影响这些疾病的发展和恢复。在盲肠泥浆 (CS) 诱导的脓毒症小鼠模型中，我们进行了三种不同的行为测试，即露天试验、大理石埋藏试验和强迫游泳试验，并观察了脓毒症小鼠的焦虑样行为。此外，增加的白介素 (IL)-1β 和 IL-6 表达水平，在脓毒症发作后 10 天，在脓毒症小鼠的大脑中检查了嗜中性粒细胞和 T 细胞的浸润情况。脓毒症发作 20 天后，脓毒症小鼠可以恢复星形胶质细胞的数量。在第 30 天，脓毒症小鼠大脑皮层中 IL-1β 和肿瘤坏死因子 (TNF)-α 的表达水平恢复到正常水平。有趣的是，在用 FTY720 治疗的脓毒症小鼠中，神经炎症的消退和抑郁症的缓解被延迟，FTY720 抑制了 1-磷酸鞘氨醇 (S1P) 依赖性淋巴细胞从淋巴结流出。在分析脓毒症小鼠有或没有 FTY720 的脑 T 细胞时，未经 FTY720 治疗的小鼠在大脑中表现出增加的调节性 T 细胞（Treg）和 Th2 细胞，而经 FTY720 治疗的小鼠在第 30 天表现出增加的脑中 Th17。此外，在 FTY720 处理的败血症小鼠中，