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The Role of the Microbiota in Acute Stress-Induced Myeloid Immune Cell Trafficking
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.bbi.2019.12.003
Marcel van de Wouw 1 , Joshua M Lyte 1 , Marcus Boehme 1 , Marzia Sichetti 2 , Gerard Moloney 3 , Michael S Goodson 4 , Nancy Kelley-Loughnane 4 , Timothy G Dinan 5 , Gerard Clarke 5 , John F Cryan 3
Affiliation  

There has been a growing recognition of the involvement of the gastrointestinal microbiota in the development of stress-related disorders. Acute stress leads to activation of the neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells. Both these response systems are independently known to be primed by the microbiota, even though much is still unclear about the role of the gastrointestinal microbiota in acute stress-induced immune activation. In this study, we investigated whether the microbiota influences acute stress-induced changes in innate immunity using conventionally colonised mice, mice devoid of any microbiota (i.e. germ-free, GF), and colonised GF mice (CGF). We also explored the kinetics of stress-induced immune cell mobilisation in the blood, the spleen and mesenteric lymph nodes (MLNs). Mice were either euthanised prior to stress or underwent restraint stress and were then euthanised at various time points (i.e. 0, 45- and 240-minutes) post-stress. Plasma adrenaline and noradrenaline levels were analysed using ELISA and immune cell levels were quantified using flow cytometry. GF mice had increased baseline levels of adrenaline and noradrenaline, of which adrenaline was normalised in CGF mice. In tandem, GF mice had decreased circulating levels of LY6Chi and LY6Cmid, CCR2+ monocytes, and granulocytes, but not LY6C-, CX3CR1+ monocytes. These deficits were normalised in CGF mice. Acute stress decreased blood LY6Chi and LY6Cmid, CCR2+ monocytes while increasing granulocyte levels in all groups 45 minutes post-stress. However, only GF mice showed stress-induced changes in LY6Chi monocytes and granulocytes 240 minutes post-stress, indicating impairments in the recovery from acute stress-induced changes in levels of specific innate immune cell types. LY6C-, CX3CR1+ monocytes remained unaffected by stress, indicating that acute stress impacts systemic innate immunity in a cell-type-specific manner. Overall, these data reveal novel cell-type-specific changes in the innate immune system in response to acute stress, which in turn are impacted by the microbiota. In conclusion, the microbiota influences the priming and recovery of the innate immune system to an acute stressor and may inform future microbiota-targeted therapeutics aimed at modulating stress-induced immune activation in stress-related disorders.

中文翻译:

微生物群在急性应激诱导的骨髓免疫细胞贩运中的作用

人们越来越认识到胃肠道微生物群与压力相关疾病的发展有关。急性压力会导致神经内分泌系统的激活,进而协调先天免疫细胞的大规模重新分布。尽管胃肠道微生物群在急性应激诱导的免疫激活中的作用尚不清楚,但已知这两种反应系统都是由微生物群引发的。在这项研究中,我们使用常规定植的小鼠、没有任何微生物群的小鼠(即无菌、GF)和定植的 GF 小鼠(CGF)研究了微生物群是否影响急性应激诱导的先天免疫变化。我们还探索了血液、脾脏和肠系膜淋巴结 (MLN) 中应激诱导的免疫细胞动员的动力学。小鼠要么在应激前被安乐死,要么经受束缚应激,然后在应激后的不同时间点(即 0、45 和 240 分钟)安乐死。使用 ELISA 分析血浆肾上腺素和去甲肾上腺素水平,并使用流式细胞术定量免疫细胞水平。GF 小鼠的肾上腺素和去甲肾上腺素的基线水平增加,其中肾上腺素在 CGF 小鼠中正常化。同时,GF 小鼠的 LY6Chi 和 LY6Cmid、CCR2+ 单核细胞和粒细胞的循环水平降低,但 LY6C-、CX3CR1+ 单核细胞没有降低。这些缺陷在 CGF 小鼠中正常化。在压力后 45 分钟,急性压力降低了所有组的血液 LY6Chi 和 LY6Cmid、CCR2+ 单核细胞,同时增加了粒细胞水平。然而,只有 GF 小鼠在应激后 240 分钟表现出应激诱导的 LY6Chi 单核细胞和粒细胞变化,表明从急性应激引起的特定先天免疫细胞类型水平变化的恢复受损。LY6C-、CX3CR1+ 单核细胞不受压力影响,表明急性压力以细胞类型特异性方式影响全身先天免疫。总体而言,这些数据揭示了先天免疫系统响应急性压力的新型细胞类型特异性变化,而后者又受到微生物群的影响。总之,微生物群影响先天免疫系统对急性应激源的启动和恢复,并可能为未来旨在调节应激相关疾病中应激诱导的免疫激活的微生物群靶向治疗提供信息。表明急性应激以细胞类型特异性方式影响全身先天免疫。总体而言,这些数据揭示了先天免疫系统响应急性压力的新型细胞类型特异性变化,而后者又受到微生物群的影响。总之,微生物群影响先天免疫系统对急性应激源的启动和恢复,并可能为未来旨在调节应激相关疾病中应激诱导的免疫激活的微生物群靶向治疗提供信息。表明急性应激以细胞类型特异性方式影响全身先天免疫。总体而言,这些数据揭示了先天免疫系统响应急性压力的新型细胞类型特异性变化,而后者又受到微生物群的影响。总之,微生物群影响先天免疫系统对急性应激源的启动和恢复,并可能为未来旨在调节应激相关疾病中应激诱导的免疫激活的微生物群靶向治疗提供信息。
更新日期:2020-02-01
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