The Immunological Puzzle of Atlantic Cod: Thriving Without MHC II

Title: The Immunological Puzzle of Atlantic Cod: Thriving Without MHC II Francisellosis is a bacterial infection caused by Francisella noatunensis subsp noatunensis (F.n.n) in teleosts such as Atlantic cod (Gadus morhua). These vulnerable Atlantic cods are crucial for sustainability of the North Atlantic ecosystem and fisheries. The disease is generally manifested as granulomatous lesions in head, kidney, liver, gills, heart and spleen. At present, its treatment is a major challenges for commercial fisheries sectors with the current availability of only antibacterial drugs with limited efficacy and no licensed vaccine available for the fish, so far. Genome sequencing of Atlantic cod revealed lack of otherwise well conserved among other vertebrates, the major histocompatibility complex (MHC) class II immune pathway due to gene losses of MHC II, CD4 and invariant chain (Ii) and presence of an expanded MHC I and toll-like receptor (TLR) repertoire. Little is known for the compensatory mechanisms governing immune responses against infections in the cod, in the absence of MHC II. We aim to determine the functions of MHC I and TLRs and mechanisms of antigen presentation and immune responses to bacterial infection in the cod fish with 2 objectives 1) characterization of MHCs and TLRs using teleosts as model systems b) identify the mechanisms of bacterial infection involving MHCs and TLRs. The methodologies involve culturing of wild caught Atlantic cod derived primary macrophages and cell lines, transfection with fluorescently labelled MHCs and TLRs, microscopy (live-cell imaging, super-resolution microscopy), RUSH assays, mass spectrometry, pull down assays, transcriptomics to elucidate the role of different MHC I and TLRs in response to F.n.n infection. This will enable us to delineate expanded roles of MHC I and TLRs and provide a platform to develop effective antibacterial therapeutic strategies against F.n.n infection in Atlantic cods.