TLR4 is a target of environmentally relevant concentration of lead

Lead (Pb) alters the susceptibility to different pathogens suggesting that macrophage-mediated defense mechanisms, through activation of toll-like receptors (TLRs), may be affected by Pb. The aim of this study was to test whether activation of TLR4 is a targeted molecule to the effect of environmentally relevant Pb concentrations (0.05, 0.5 and 5 μg/dL). The function of macrophages activated through TLR4 was evaluated using as TLR4 ligand lipopolysaccharides (LPSs) from two different pathogens: Escherichia coli and Salmonella typhimurium. Pb induced proliferation, increased the NO− baseline, IL-1β and IL-6 secretion. Interestingly, Pb exposure induced differential effects on cells stimulated with the two LPS used: in macrophages stimulated with LPS from E. coli, Pb caused an early decrease in proliferation, increase NO− production, and decrease IL-6 and TNF-α secretion; in macrophages stimulated with LPS from S. typhimurium, Pb decreased proliferation after 36 h, induced a biphasic effect on NO− production, and enhance the secretion of IL-1β, IL-6 and TNF-α. Results suggest that TLR4 is a target for the Pb effect, which up to 5.0 μg/dL affect immune competence against pathogens, dependent on the bacterial species. This effect may be attributable to structural differences that determine LPS affinity for TLR4.

► TLR4 is a target to the effect of concentrations ≤5 μg/dL of Pb. ► Pb at concentrations up to 5 μg/dL induces IL-1β and IL-6 in macrophages. ► The Pb differential affect macrophages stimulated with LPSs from two pathogens. ► Pb effect on TLR4 may be related to decrease in response to infections. ► The Pb effect on macrophages is dependent of affinity of LPS by the TLR4.