Interdisciplinary Faculty of Toxicology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States.
Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States.
Front Immunol. 2023 Aug 2;14:1228509. doi: 10.3389/fimmu.2023.1228509. eCollection 2023.
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.
神经疾病可能源于环境影响，如先前的病毒感染或接触潜在的毒物，其中一些可能引发免疫反应，导致神经症状。Theiler's 鼠脑脊髓炎病毒（TMEV）被用于模拟与先前病毒感染相关的人类神经状况，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）可改变已知影响神经疾病的病理学，如炎症反应、细胞因子表达和神经胶质细胞激活。TMEV 和 PFOA 的共同暴露用于检验假设，即早期生活中暴露于潜在免疫毒性的 PFOA 将影响免疫反应，从而使 TMEV 抗性 C57BL/6J（B6）小鼠易患病毒引起的神经疾病。
新生 B6 小鼠接受不同处理：非注射、用 PBS 假感染和 TMEV 感染，每组的饮用水包括 70 ppt PFOA 或过滤水。通过比较病毒感染引起的神经症状和免疫相关细胞因子和趋化因子产生的变化来评估 PFOA 的影响。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，暴露于 PFOA 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，在未感染组中恢复了平衡，特征是促炎细胞因子增加，而在 PFOA+TMEV 组中 IL-10 减少。此外，PFOA+TMEV 组的癫痫发作频率和严重程度增加。
总体而言，这些发现提供了对免疫反应在病毒相关神经疾病发病机制中的复杂作用的深入了解，这些疾病受病毒和免疫毒性化合物共同暴露的影响。
