The myxozoan parasite Tetracapsuloides bryosalmonae is the causative agent of proliferative kidney disease (PKD)-a disease of salmonid fishes, notably of the commercially farmed rainbow trout Oncorhynchus mykiss. Both wild and farmed salmonids are threatened by this virulent/deadly disease, a chronic immunopathology characterized by massive lymphocyte proliferation and hyperplasia, which manifests as swollen kidneys in susceptible hosts. Studying the immune response towards the parasite helps us understand the causes and consequences of PKD. While examining the B cell population during a seasonal outbreak of PKD, we unexpectedly detected the B cell marker immunoglobulin M (IgM) on red blood cells (RBCs) of infected farmed rainbow trout. Here, we studied the nature of this IgM and this IgM+ cell population. We verified the presence of surface IgM via parallel approaches: flow cytometry, microscopy, and mass spectrometry. The levels of surface IgM (allowing complete resolution of IgM- RBCs from IgM+ RBCs) and frequency of IgM+ RBCs (with up to 99% of RBCs being positive) have not been described before in healthy fishes nor those suffering from disease. To assess the influence of the disease on these cells, we profiled the transcriptomes of teleost RBCs in health and disease. Compared to RBCs originating from healthy fish, PKD fundamentally altered RBCs in their metabolism, adhesion, and innate immune response to inflammation. In summary, RBCs play a larger role in host immunity than previously appreciated. Specifically, our findings indicate that the nucleated RBCs of rainbow trout interact with host IgM and contribute to the immune response in PKD.

Core Facility for Microarray Analysis Institute for Immunology Rostock University Medical Centre Rostock Germany

Division of Fish Health Veterinary University of Vienna Vienna Austria

Faculty of Science University of South Bohemia České Budějovice Czechia

Fish Genetics Unit Institute of Genome Biology Research Institute for Farm Animal Biology Dummerstorf Germany

Laboratory of Fish Protistology Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czechia

South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses Institute of Aquaculture and Protection of Waters Faculty of Fisheries and Protection of Waters University of South Bohemia České Budějovice Czechia

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