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Elevated levels of lead have been found in waterfowl, due to human activities. Lead may cause immunomodulatory effects, but the mechanisms are largely unknown, especially after viral challenges. To characterize avian immunomodulatory hazards of lead (Pb) 2+ , we used chicken macrophage (HD‐11) and B‐lymphocyte (DT40) cell lines, as in vitro models for the innate and adaptive immune systems, respectively. The cells were activated via toll‐like receptor‐3 by polyinosinic–polycytidylic acid sodium salt (poly I:C), mimicking viral infections. Our results indicate that Pb 2+  is cytotoxic to both cell lines, macrophages being more sensitive. De novo synthesis of glutathione plays an important role in protecting macrophages from Pb 2+  intoxication, which might also be closely involved in the induction of nitric oxide after Pb 2+  exposure. Stimulatory effects on cell proliferation were noticed at noncytotoxic Pb 2+  concentrations as well. Exposure to Pb 2+  could also affect the inflammatory status by inhibiting the pro‐inflammatory interferon (IFN)‐γ while promoting the production of anti‐inflammatory type I IFNs in both macrophages and B‐cells, and increasing intracellular IgM levels in B‐cells. These results suggest that the immunomodulatory effects of Pb 2+  in birds are probably closely associated with disruption of immune cell proliferation and cytokine production, potentially causing disorders of the avian immune system.  Environ Toxicol Chem  2020;39:1060–1070. © 2020 The Authors.  Environmental Toxicology and Chemistry  published by Wiley Periodicals LLC

Modulatory Effects of Pb 2+ on Virally Challenged Chicken Macrophage (HD‐11) and B‐Lymphocyte (DT40) Cell Lines In Vitro