Psychological stress creates an immune suppressive environment in the lung that increases susceptibility of aged mice to Mycobacterium tuberculosis infection.
Psychological stress creates an immune suppressive environment in the lung that increases susceptibility of aged mice to Mycobacterium tuberculosis infection.
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DOI：
10.3389/fcimb.2022.990402
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发表时间：
2022
影响因子：
5.7
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中科院分区：
文献类型：
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年龄是包括结核病在内的慢性感染的主要危险因素。老年结核病患者也遭受更高水平的心理压力。目前尚不清楚心理压力如何影响对结核分枝杆菌（M.tb）的免疫反应。在这项研究中，我们使用社会破坏压力（SDR）的心理应激的影响，在年轻和老年小鼠。出乎意料的是，我们发现SDR抑制了老年小鼠的肺部炎症，这一点可以通过支气管灌洗液中促炎细胞因子水平降低和肺泡巨噬细胞的细胞因子mRNA表达降低来证明。为了研究应激对结核分枝杆菌感染的影响，使小鼠经受SDR，然后用结核分枝杆菌感染。如前所述，老年小鼠在30天内比年轻小鼠更好地控制感染。该对照是短暂的，因为与年轻小鼠相比，老年对照小鼠在60天时的CFU更高。一致地，与年轻小鼠相比，SDR显著增加老年小鼠中60天时的结核分枝杆菌生长。另外，老年小鼠SDR后60 d IL-10 mRNA表达增加，IFN-γ mRNA表达下降。此外，来自老年SDR小鼠的肺切片的共聚焦显微镜显示表达LAG 3和CD 49 b（分泌IL-10的调节性T细胞的标志物）的CD 4 T细胞的数量增加。此外，我们还证明了来自老年SDR小鼠的CD 4 T细胞表达IL-10。因此，我们得出结论，老年小鼠在感染前的心理应激增加了分泌IL-10的T细胞的分化，这随着时间的推移导致感染失控。
Age is a major risk factor for chronic infections, including tuberculosis (TB). Elderly TB patients also suffer from elevated levels of psychological stress. It is not clear how psychological stress impacts immune response to Mycobacterium tuberculosis (M.tb). In this study, we used social disruption stress (SDR) to investigate effects of psychological stress in young and old mice. Unexpectedly, we found that SDR suppresses lung inflammation in old mice as evidenced by lower pro-inflammatory cytokine levels in bronchial lavage fluid and decreased cytokine mRNA expression by alveolar macrophages. To investigate effects of stress on M.tb infection, mice were subjected to SDR and then infected with M.tb. As previously reported, old mice were better at controlling infection at 30 days than young mice. This control was transient as CFUs at 60 days were higher in old control mice compared to young mice. Consistently, SDR significantly increased M.tb growth at 60 days in old mice compared to young mice. In addition, SDR in old mice resulted in accumulation of IL-10 mRNA and decreased IFN-γ mRNA at 60 days. Also, confocal microscopy of lung sections from old SDR mice showed increased number of CD4 T cells which express LAG3 and CD49b, markers of IL-10 secreting regulatory T cells. Further, we also demonstrated that CD4 T cells from old SDR mice express IL-10. Thus, we conclude that psychological stress in old mice prior to infection, increases differentiation of IL-10 secreting T cells, which over time results in loss of control of the infection.