Mercury (Hg) is a toxic trace metal ubiquitously distributed in the environment. Inorganic mercury (as HgCl₂) can cause immunotoxicity in birds, but the mechanisms of action are still not fully resolved, especially with respect to responses to viral infections. To investigate the potential immunomodulatory effects of Hg²⁺ on specific cell types of the avian immune system, chicken macrophage (HD-11) and B-lymphocyte (DT40) cell lines were applied as in vitro models for the innate and adaptive immune systems, respectively. The cells were stimulated with synthetic double-stranded RNA, which can be recognized by toll-like receptor-3 to mimic a viral infection. The Hg²⁺ showed concentration-dependent cytotoxicity in both cell lines, with similar median effect concentrations at 30 µM. The cytotoxicity of Hg²⁺ was closely related to glutathione (GSH) depletion and reactive oxygen species induction, whereas the de novo synthesis of GSH acted as a primary protective strategy. Nitric oxide produced by activated macrophages was strongly inhibited by Hg²⁺, and was also influenced by cellular GSH levels. Cell proliferation, gene expression of microRNA-155, and cellular IgM levels in B cells were decreased at noncytotoxic Hg²⁺ concentrations. The secretion of antiviral interferon-α was induced by Hg²⁺ in both cell lines. Overall, our results suggest that Hg²⁺ exposure can cause immunomodulatory effects in birds by disrupting immune cell proliferation and cytokine production, and might result in disorders of the avian immune system. Environ Toxicol Chem 2021;40:2813–2824. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

中文翻译：

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汞 (II) 氯化物 (HgCl2) 对鸡巨噬细胞和 B 淋巴细胞细胞系的调节作用，在体外具有病毒样挑战

汞 (Hg) 是一种有毒的微量金属，广泛分布于环境中。无机汞（如 HgCl ₂）可在鸟类中引起免疫毒性，但作用机制仍未完全解决，特别是在对病毒感染的反应方面。为了研究 Hg ²⁺对禽类免疫系统特定细胞类型的潜在免疫调节作用，将鸡巨噬细胞 (HD-11) 和 B 淋巴细胞 (DT40) 细胞系用作先天性和适应性免疫系统的体外模型，分别。用合成的双链 RNA 刺激细胞，这种 RNA 可以被 toll 样受体 3 识别以模拟病毒感染。汞²⁺在两种细胞系中均显示出浓度依赖性细胞毒性，在 30 µM 时具有相似的中值效应浓度。Hg ²⁺的细胞毒性与谷胱甘肽 (GSH) 的消耗和活性氧的诱导密切相关，而 GSH 的从头合成是主要的保护策略。由活化的巨噬细胞产生的一氧化氮受到Hg ²⁺的强烈抑制，并且还受细胞GSH水平的影响。^{在非细胞毒性 Hg 2+}浓度下，B 细胞中的细胞增殖、microRNA-155 基因表达和细胞 IgM 水平降低。^{Hg 2+}在两种细胞系中均诱导抗病毒干扰素-α的分泌。总的来说，我们的结果表明 Hg ²⁺暴露可通过破坏免疫细胞增殖和细胞因子产生对鸟类产生免疫调节作用，并可能导致鸟类免疫系统紊乱。环境毒物化学2021；40:2813–2824。© 2021 作者。Wiley Periodicals LLC 代表 SETAC 出版的Environmental Toxicology and Chemistry 。