Induced‑iron overdose modulate the immune response in Atlantic salmon increasing the susceptibility to Piscirickettsia salmonis infection

Although iron has been proved as a vital element for the development of living organisms, high levels of this element can impact the normal function of different biological processes, including immune response. Therein, this study aimed to characterize the transcriptional changes in Atlantic salmon during the exposure to iron overload, evaluating the susceptibility to bacterial infection. Atlantic salmon were injected with 1 or 5 mg of iron dextran and an iron chelator (DFOM), and subsequently challenged with the intracellular bacterium Piscirickettsia salmonis. Iron levels in plasma and the transcriptional responses of the head kidney, liver, and spleen during the infection processes were evaluated. Here, iron transport, response to oxidative stress, and immune related genes were strongly modulated in individuals exposed to the metal. Fish overloaded with iron showed significant downregulation of CD83, IL-17, IL-1, Toll-like receptors, immunoglobulin, and T-cell receptors genes, suggesting an overall deleterious effect on the immune system. Furthermore, histopathological analysis evidenced that iron overdoses can strongly increase the clinical signs during the P. salmonis infection. Notably, fish exposed to 1 mg of iron and infected with P. salmonis evidenced high mortality and bacterial burden. Also, this group showed significant downregulation of immune-related genes comparing with fish with 5 mg of iron. In addition, Atlantic salmon injected with deferoxamine mesylate salt (DFOM) showed high tolerance to P. salmonis infection and an increase of IL-1b expression, suggesting a cytokines response activation. These results suggest that iron overload disrupts fish immune response although not in a doses dependent manner, and when a chelator is injected, fish present higher resistance to P. salmonis. This study reveals novel insights about teleost's immune system modulation by iron availability.