Chronic psychosocial stress is a risk factor for many mental disorders, including affective disorders, anxiety disorders, and trauma- and stressor-related disorders (i.e. posttraumatic stress disorder, PTSD). As these disorders are associated with an overreactive immune system and chronic low-grade inflammation, immunoregulatory approaches counterbalancing basal and/or stress-induced immune activation should be protective in this context. In support of this hypothesis, we recently demonstrated that repeated subcutaneous (s.c) preimmunization with a heat-killed preparation of the immunoregulatory bacterium Mycobacterium vaccae (M. vaccae; National Collection of Type Culture (NCTC) 11659) promoted proactive stress coping and protected against stress-induced anxiety and intestinal pathology in a mouse model of chronic psychosocial stress. To induce development of a chronic anxiety-like state, the chronic subordinate colony housing (CSC) paradigm was used. Here we employed the CSC paradigm (start day 1) to confirm the stress-protective effects of repeated s.c. M. vaccae administrations prior to CSC exposure (days -21, -14, and -7) and to extend these findings to the stress-protective role of M. vaccae when administered repeatedly during CSC exposure (days 2, 8 and 15). As readouts we assessed the stress coping behavior on days 1, 8, and 15 and general and/or social anxiety-related behavior on days 19 (elevated plus-maze), 20 (open-field/novel object test) and day 21 (social preference/avoidance test) of CSC exposure. In line with our previous study, M. vaccae administered prior to CSC strongly promoted active stress coping and moderately reduced CSC-induced general and social anxiety. Although M. vaccae administered during CSC did not affect stress coping, this treatment protocol profoundly protected against CSC-induced general, and to a lesser extent social, anxiety. Taken together, these data broaden the framework for developing bioimmunoregulatory approaches, based on the administration of immunoregulatory microorganisms, for the prevention and/or treatment of affective disorders, anxiety disorders, and trauma- and stressor-related psychiatric disorders like PTSD.

中文翻译：

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在心理社会压力之前或期间给予皮下母牛分枝杆菌可促进慢性心理社会压力小鼠模型的恢复力

慢性社会心理压力是许多精神障碍的危险因素，包括情感障碍、焦虑障碍以及与创伤和压力源相关的障碍（即创伤后应激障碍，PTSD）。由于这些疾病与过度反应的免疫系统和慢性低度炎症有关，在这种情况下，平衡基础和/或压力诱导的免疫激活的免疫调节方法应该是保护性的。为支持这一假设，我们最近证明，使用免疫调节细菌母牛分枝杆菌（母牛分枝杆菌；国家典型培养物保藏中心 (NCTC) 11659）的热灭活制剂重复皮下 (sc) 预免疫可促进主动应对压力并预防慢性心理社会压力小鼠模型中的压力引起的焦虑和肠道病理。为了诱导慢性焦虑样状态的发展，使用了慢性从属殖民地住房 (CSC) 范式。在这里，我们采用 CSC 范式（从第 1 天开始）来确认在 CSC 暴露（第 -21、-14 和 -7 天）之前重复施用 sc M. vaccae 的压力保护作用，并将这些发现扩展到压力 -在 CSC 暴露期间（第 2、8 和 15 天）重复给药时母牛分枝杆菌的保护作用。作为读数，我们评估了第 1、8 和 15 天的压力应对行为以及第 19 天（高架十字迷宫）、第 20 天（露天/新物体测试）和第 21 天（ CSC 暴露的社会偏好/回避测试）。与我们之前的研究一致，M。在 CSC 之前施用的 vaccae 强烈促进了积极的压力应对，并适度减少了 CSC 引起的一般和社交焦虑。尽管在 CSC 期间施用的母牛分枝杆菌不影响压力应对，但这种治疗方案可以有效地防止 CSC 引起的一般性焦虑，并在较小程度上防止社交焦虑。总之，这些数据拓宽了开发基于免疫调节微生物的生物免疫调节方法的框架，用于预防和/或治疗情感障碍、焦虑症以及与创伤和压力相关的精神障碍（如 PTSD）。