Chronically elevated cortisol levels increase cognate pathogen load but reduce red mark syndrome pathology in rainbow trout (Oncorhynchus mykiss)

Red mark syndrome (RMS) is a non-lethal skin disease affecting rainbow trout. Hallmark symptoms of the disease are one or few large, well-defined areas with oedema, hyperaemia and often scale resorption. The pathology is associated with a massive lymphohistiocytic infiltrate with a predominance of B cells. The disease is caused by an obligate intracellular bacterium in the order Rickettsiales. We hypothesized that the pathology is host-driven and that attenuating the immune response would result in reduced pathology. To test this hypothesis, we mimicked the immunosuppressive effect of chronic physiological stress through intraperitoneal injection of slow-release cortisol implants into rainbow trout subjected to the disease by cohabitation. The fish were kept at 12 °C. After 70 days of cohabitation the fish had developed pathology, and the experiment was terminated and fish sampled. Fish with cortisol implants had elevated cortisol levels compared to fish injected with control implants. This elevation in serum cortisol levels was accompanied by milder RMS pathology, but with higher levels of cognate pathogen. Expression analysis on 30 immune-related genes showed that the chronic stress proxy broadly resulted in reduced transcript levels in skin, especially of B and T cell-associated genes. However, this effect was only observed for asymptomatic skin. At skin sites with RMS pathology, transcription levels of most of the genes investigated were largely unaffected by cortisol treatment with some exceptions: Cortisol-treated fish had reduced transcription levels of membrane-bound immunoglobulin M (mIgM) and D (mIgD), and increased transcription levels of genes involved in inflammation and cell-mediated cytotoxicity (e.g. IL-1β, IFN-γ, NKEF and granzyme A). Thus, in RMS lesions the immunosuppressive effect of cortisol on B cells was less evident. In conclusion, the fact that immunosuppressed fish harboured more pathogen despite appearing less affected by the disease strongly indicates that RMS is a host-driven disease.