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

Abstract

Mercury (Hg) is a toxic trace metal ubiquitously distributed in the environment. Inorganic mercury (as HgCl 2 ) 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 Hg 2+ 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 Hg 2+ showed concentration-dependent cytotoxicity in both cell lines, with similar median effect concentrations at 30 µM. The cytotoxicity of Hg 2+ 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 Hg 2+ , 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 Hg 2+ concentrations. The secretion of antiviral interferon-α was induced by Hg 2+ in both cell lines. Overall, our results suggest that Hg 2+ 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.

Mercury-Modulated Immune Responses in Arctic Barnacle Goslings (Branta leucopsis) upon a Viral-Like Immune Challenge

“…For example, abnormally high levels of heterophils were found in American kestrels (Falco sparverius) exposed to Hg, while reduced CD4+ lymphocyte counts were reported in Hg-exposed workers . In vitro exposure to HgCl 2 inhibited the proliferation of immune cell lines from both chicken ( Gallus gallus domesticus ) and murine species, as well as primary lymphocytes from mice (Mus musculus), beluga whales, snakes (Nerodia taxispilota), and humans (Homo sapiens) . Different sensitivities of immune cell types to Hg exposure may explain the change in immune cell composition …”

“…83 Different sensitivities of immune cell types to Hg exposure may explain the change in immune cell composition. 79 Oxidative Stress. Hg is reported to have a high affinity for the thiol group in GSH 84 and could induce the conversion of GSH to its oxidized form glutathione disulfide (GSSG), disturbing the redox balance and resulting in oxidative stress.…”

“…In vitro exposure to HgCl 2 inhibited the proliferation of immune cell lines from both chicken ( Gallus gallus domesticus ) and murine species, as well as primary lymphocytes from mice (Mus musculus), beluga whales, snakes (Nerodia taxispilota), and humans (Homo sapiens) . Different sensitivities of immune cell types to Hg exposure may explain the change in immune cell composition …”

“… 83 Different sensitivities of immune cell types to Hg exposure may explain the change in immune cell composition. 79 …”

Modulatory effects of divalent mercury and lead on the immune responses of waterfowl upon a viral-like immune challenge

“…The results showed a clear dose-dependent relationship of internal tHg concentrations and miR-155 expression, where miR-155 expression was strongly suppressed at hepatic tHg concentrations higher than 1 mg/kg d.w.(Figure 3.2e). Downregulation of miR-155 was also noticed in a Hg(II) exposed chicken B-cell line in vitro (Han et al, 2021). Decreased miR-155 levels could cause impaired B-cell function and anti-viral immunity Mehta & Baltimore, 2016;.…”