C57BL/6J mice exposed to perfluorooctanoic acid demonstrate altered immune responses and increased seizures after Theiler's murine encephalomyelitis virus infection.
C57BL/6J mice exposed to perfluorooctanoic acid demonstrate altered immune responses and increased seizures after Theiler's murine encephalomyelitis virus infection.
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DOI：
10.3389/fimmu.2023.1228509
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
神经系统疾病可能源于环境影响，例如先前的病毒感染或接触潜在的有毒物质，其中一些可能触发免疫反应，导致神经系统症状。泰勒氏鼠脑脊髓炎病毒 (TMEV) 用于模拟与先前病毒感染相关的人类神经系统疾病，其结果部分归因于免疫反应的不当诱导和调节。全氟辛酸 (PFOA) 可以改变已知影响神经系统疾病的病理，例如炎症反应、细胞因子表达和神经胶质活化。共同暴露于 TMEV 和 PFOA 用于检验以下假设：生命早期暴露于潜在的免疫毒性物质 PFOA 会影响免疫反应，从而使 TMEV 耐药的 C57BL/6J (B6) 小鼠易患病毒引起的神经系统疾病。新生 B6 小鼠接受不同的处理：未注射、PBS 假感染和 TMEV 感染，每组的饮用水包括 70 ppt PFOA 或过滤水。通过比较神经系统症状以及病毒感染引起的免疫相关细胞因子和趋化因子产生的变化来评估 PFOA 的作用。在感染前后测量 23 种细胞因子和趋化因子的免疫反应，以确定 PFOA 暴露对免疫反应的影响。在感染之前，在 PFOA 暴露的小鼠中观察到 Th1、Th2 和 Treg 细胞因子之间的不平衡，抑制了 IL-4 和 IL-13 的产生。然而，平衡得到恢复，其特征是未感染组促炎细胞因子增加，PFOA + TMEV 组 IL-10 减少。此外，PFOA + TMEV 组的癫痫发作频率和严重程度有所增加。总体而言，这些发现提供了关于免疫反应在病毒相关神经系统疾病发病机制中的复杂作用的见解，这些疾病受病毒和免疫毒性化合物的共同暴露影响。
Neurological diseases can stem from environmental influences such as antecedent viral infections or exposure to potential toxicants, some of which can trigger immune responses leading to neurological symptoms. Theiler’s murine encephalomyelitis virus (TMEV) is used to model human neurological conditions associated with prior viral infections, with outcomes partly attributable to improper induction and regulation of the immune response. Perfluorooctanoic acid (PFOA) can alter pathologies known to influence neurological disease such as inflammatory responses, cytokine expression, and glial activation. Co-exposure to TMEV and PFOA was used to test the hypothesis that early life exposure to the potential immunotoxicant PFOA would affect immune responses so as to render TMEV-resistant C57BL/6J (B6) mice susceptible to viral-induced neurological disease. Neonate B6 mice were exposed to different treatments: non-injected, sham-infected with PBS, and TMEV-infected, with the drinking water of each group including either 70 ppt PFOA or filtered water. The effects of PFOA were evaluated by comparing neurological symptoms and changes in immune-related cytokine and chemokine production induced by viral infection. Immune responses of 23 cytokines and chemokines were measured before and after infection to determine the effects of PFOA exposure on immune response. Prior to infection, an imbalance between Th1, Th2, and Treg cytokines was observed in PFOA-exposed mice, suppressing IL-4 and IL-13 production. However, the balance was restored and characterized by an increase in pro-inflammatory cytokines in the non-infected group, and a decrease in IL-10 in the PFOA + TMEV group. Furthermore, the PFOA + TMEV group experienced an increase in seizure frequency and severity. Overall, these findings provide insight into the complex roles of immune responses in the pathogenesis of virus-associated neurological diseases influenced by co-exposures to viruses and immunotoxic compounds.
影响因子：
6
作者：
通讯作者：
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影响因子：
5.6
作者：
Brinkmeyer-Langford C;Amstalden K;Konganti K;Hillhouse A;Lawley K;Perez-Gomez A;Young CR;Welsh CJ;Threadgill DW
通讯作者：
Threadgill DW
DOI：
10.1016/j.bbih.2021.100395
发表时间：
2021-12
期刊：
Brain, behavior, & immunity - health
影响因子：
--
作者：
Perez Gomez AA;Karmakar M;Carroll RJ;Lawley KS;Amstalden K;Young CR;Threadgill DW;Welsh CJ;Brinkmeyer-Langford C
通讯作者：
Brinkmeyer-Langford C