AUTHOR=Gnanagobal Hajarooba , Cao Trung , Hossain Ahmed , Dang My , Hall Jennifer R. , Kumar Surendra , Van Cuong Doan , Boyce Danny , Santander Javier 

TITLE=Lumpfish (Cyclopterus lumpus) Is Susceptible to Renibacterium salmoninarum Infection and Induces Cell-Mediated Immunity in the Chronic Stage

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.733266

DOI=10.3389/fimmu.2021.733266

ISSN=1664-3224

ABSTRACT=<p><italic>Renibacterium salmoninarum</italic> is a Gram-positive, intracellular pathogen that causes Bacterial Kidney Disease (BKD) in several fish species in freshwater and seawater. Lumpfish (<italic>Cyclopterus lumpus</italic>) is utilized as a cleaner fish to biocontrol sea lice infestation in Atlantic salmon (<italic>Salmo salar</italic>) farms. Atlantic salmon is susceptible to <italic>R. salmoninarum</italic>, and it can transfer the infection to other fish species. Although BKD outbreaks have not been reported in lumpfish, its susceptibility and immune response to <italic>R. salmoninarum</italic> is unknown. In this study, we evaluated the susceptibility and immune response of lumpfish to <italic>R. salmoninarum</italic> infection. Groups of lumpfish were intraperitoneally (i.p.) injected with either <italic>R. salmoninarum</italic> (1×10<sup>7</sup>, 1×10<sup>8</sup>, or 1×10<sup>9</sup> cells dose<sup>-1</sup>) or PBS (control). <italic>R. salmoninarum</italic> infection kinetics and mortality were followed for 98 days post-infection (dpi). Transcript expression levels of 33 immune-relevant genes were measured in head kidney (<italic>n</italic> = 6) of fish infected with 1×10<sup>9</sup> cells/dose and compared to the control at 28 and 98 dpi. Infected lumpfish displayed characteristic clinical signs of BKD. Lumpfish infected with high, medium, and low doses had a survival rate of 65%, 93%, and 95%, respectively. Mortality in the high-dose infected group stabilized after 50 dpi, but <italic>R. salmoninarum</italic> persisted in the fish tissues until 98 dpi. Cytokines (<italic>il1β</italic>, <italic>il8a</italic>, <italic>il8b</italic>), pattern recognition receptors (<italic>tlr5a</italic>), interferon-induced effectors (<italic>rsad2, mxa</italic>, <italic>mxb</italic>, <italic>mxc</italic>), and iron regulation (<italic>hamp</italic>) and acute phase reactant (<italic>saa5</italic>) related genes were up-regulated at 28 dpi. In contrast, cell-mediated adaptive immunity-related genes (<italic>cd4a</italic>, <italic>cd4b</italic>, <italic>ly6g6f</italic>, <italic>cd8a</italic>, <italic>cd74</italic>) were down-regulated at 28 dpi, revealing the immune suppressive nature of <italic>R. salmoninarum</italic>. However, significant upregulation of <italic>cd74</italic> at 98 dpi suggests induction of cell-mediated immune response. This study showed that <italic>R. salmoninarum</italic> infected lumpfish in a similar fashion to salmonid fish species and caused a chronic infection, enhancing cell-mediated adaptive immune response.</p>