Piscirickettsiosis causes the highest mortality in Atlantic salmon (Salmo salar) farming, and prophylactic treatment has not provided complete protection to date. In this study, we analyzed the immune and metabolic responses of Atlantic salmon inoculated with live and inactivated Piscirickettsia salmonis, monitoring plasma markers related to immune and stress responses. The fish were inoculated with inactivated P. salmonis, live P. salmonis, and culture medium (as control group). Blood and head-kidney samples were collected on days 3, 7, and 14 post-inoculations (dpi). Glucose and lactate levels did not show statistical differences, while cortisol levels increased from day 3 to day 14 in fish inoculated with live P. salmonis and only at 7 dpi in those inoculated with inactivated P. salmonis. Furthermore, anti-P. salmonis IgM-type immunoglobulins increased up to 14 dpi in fish inoculated with live P. salmonis but showed no change in those inoculated with inactivated P. salmonis. Meanwhile, immune markers involved in type I responses (tnfα-1, ifnγ, and cd8β) and regulatory responses (il10, tgfβ-1, and cd4-1) displayed differences between fish inoculated with live and inactivated P. salmonis. In fish inoculated with live P. salmonis, there was a clear pattern of increase at both 3 and 14 dpi, while those inoculated with inactivated P. salmonis showed a greater increase at 3 dpi. Our findings suggest that the nature of antigen may influence humoral immunity (anti-P. salmonis IgM) and the gene expression of markers involved in type I and regulatory immune responses in Atlantic salmon.

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