School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
PhD Program in Toxicology, Kaohsiung Medical University, Kaohsiung, Taiwan.
BMC Vet Res. 2024 Jan 22;20(1):30. doi: 10.1186/s12917-024-03878-3.
Fipronil (FPN) is a broad-spectrum pesticide and commonly known as low toxicity to vertebrates. However, increasing evidence suggests that exposure to FPN might induce unexpected adverse effects in the liver, reproductive, and nervous systems. Until now, the influence of FPN on immune responses, especially T-cell responses has not been well examined. Our study is designed to investigate the immunotoxicity of FPN in ovalbumin (OVA)-sensitized mice. The mice were administered with FPN by oral gavage and immunized with OVA. Primary splenocytes were prepared to examine the viability and functionality of antigen-specific T cells ex vivo. The expression of T cell cytokines, upstream transcription factors, and GABAergic signaling genes was detected by qPCR.
Intragastric administration of FPN (1-10 mg/kg) for 11 doses did not show any significant clinical symptoms. The viability of antigen-stimulated splenocytes, the production of IL-2, IL-4, and IFN-γ by OVA-specific T cells, and the serum levels of OVA-specific IgG and IgG were significantly increased in FPN-treated groups. The expression of the GABAergic signaling genes was notably altered by FPN. The GAD67 gene was significantly decreased, while the GABAR β2 and GABAR δ were increased.
FPN disturbed antigen-specific immune responses by affecting GABAergic genes in vivo. We propose that the immunotoxic effects of FPN may enhance antigen-specific immunity by dysregulation of the negative regulation of GABAergic signaling on T cell immunity.
氟虫腈（FPN）是一种广谱杀虫剂，通常被认为对脊椎动物低毒。然而，越来越多的证据表明，接触 FPN 可能会对肝脏、生殖和神经系统产生意想不到的不良影响。到目前为止，FPN 对免疫反应的影响，特别是 T 细胞反应，尚未得到充分研究。我们的研究旨在研究 FPN 对卵清蛋白（OVA）致敏小鼠的免疫毒性。通过口服灌胃给予小鼠 FPN，并免疫 OVA。制备原代脾细胞，以体外检测抗原特异性 T 细胞的活力和功能。通过 qPCR 检测 T 细胞细胞因子、上游转录因子和 GABA 能信号基因的表达。
连续 11 天经口给予 FPN（1-10mg/kg）未出现明显临床症状。FPN 处理组抗原刺激的脾细胞活力、OVA 特异性 T 细胞产生的 IL-2、IL-4 和 IFN-γ以及血清中 OVA 特异性 IgG 和 IgG 水平均显著升高。FPN 显著改变了 GABA 能信号基因的表达。GAD67 基因显著下调，而 GABARβ2 和 GABARδ上调。
FPN 通过影响体内 GABA 能基因干扰抗原特异性免疫反应。我们提出，FPN 的免疫毒性作用可能通过 GABA 能信号对 T 细胞免疫的负调节失调增强抗原特异性免疫。
