Modulatory Effects of Mercury (II) Chloride (HgCl₂) on Chicken Macrophage and B-Lymphocyte Cell Lines with Viral-Like Challenges In Vitro

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.