Department of Psychiatric Research, Diakonhjemmet Hospital, Forskningsveien 7, 0373, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Sci Rep. 2024 Mar 4;14(1):5327. doi: 10.1038/s41598-024-55887-9.
Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p < 0.001). TOXO seropositive participants had significantly higher NSE (3713 vs. 2200 pg/ml, p < 0.001) and IL-18 levels (1068 vs. 674 pg/ml, p < 0.001) than seronegative participants, and evaluation within patients and HC separately showed similar results. Post-hoc analysis on cytomegalovirus and herpes simplex virus 1 IgG status showed no associations with NSE or IL-18 which may suggest TOXO specificity. These results may indicate ongoing inflammasome activation and neuronal injury in people with TOXO infections unrelated to diagnosis.
刚地弓形虫（TOXO）感染通常会导致慢性潜伏，因为它能够在大脑和其他器官中形成囊肿。潜伏性弓形体病可能会促进先天免疫反应并影响大脑功能。大量证据表明，TOXO 感染与严重精神疾病（SMI）有关。我们假设，TOXO 免疫球蛋白 G（IgG）阳性，反映了以前的感染和当前的潜伏状态，与循环神经元特异性烯醇化酶（NSE）的增加有关，NSE 是脑损伤的标志物，以及白细胞介素-18（IL-18），一种先天免疫标志物，主要与 SMI 有关。我们纳入了 735 名 SMI 患者（精神分裂症或双相谱系）（平均年龄 32 岁，47%为女性）和 518 名健康对照者（HC）（平均年龄 33 岁，43%为女性）。用免疫测定法测量了 TOXO IgG，以表示阳性/阴性。我们搜索了 TOXO、患者/对照状态和性别对 NSE 和 IL-18 的主要和交互作用。在整个样本以及患者和 HC 中，IL-18 和 NSE 浓度呈正相关（p<0.001）。TOXO 阳性参与者的 NSE（3713 与 2200 pg/ml，p<0.001）和 IL-18 水平（1068 与 674 pg/ml，p<0.001）明显高于阴性参与者，而在患者和 HC 中分别评估时也得到了类似的结果。对巨细胞病毒和单纯疱疹病毒 1 IgG 状态的事后分析显示，与 NSE 或 IL-18 无关联，这可能表明 TOXO 的特异性。这些结果可能表明，与诊断无关的 TOXO 感染者存在持续的炎症小体激活和神经元损伤。
