Major histocompatibility complex class I (MHC Iα) of Japanese flounder (Paralichthys olivaceus) plays a critical role in defense against intracellular pathogen infection

The major histocompatibility complex (MHC) is a highly polymorphic region of the vertebrate genome that plays a critical role in initiating immune responses towards invading pathogens. It is well known that MHC I molecules play a central role in the immune response to viruses. However, rare literatures were reported the role of MHC I in the resistance to intracellular bacteria. Sequences of MHC I alpha were identified in multiple teleost species, including Japanese flounder (Paralichthys olivaceus), however, the immunological function of MHC I alpha remain largely unknown. In this study, we examined the expression profile and biological activity of an MHC I alpha homologue, PoMHC I alpha, from P. olivaceus. Structural analysis showed that PoMHC I alpha possesses conserved structural characteristics of MHC I alpha proteins, including MHC_I domain, IGc1 domain, transmembrane region. Expression of PoMHC I alpha was upregulated in a time-dependent manner by extracellular and intracellular bacterial pathogens and viral pathogen infection. Different expression patterns were exhibited in response to the infection of different types of microbial pathogens in different immune tissues. Recombinant PoMHC I alpha increased the capability of host cells to defense against intracellular pathogen Edwardsiella tarda infection and enhanced the expression of immune related genes. The knockdown of PoMHC I alpha attenuated the ability of cells to eliminate E. tarda, which was sustained by the in vivo results that overexpression of PoMHC Ia alpha promoted the host defense against invading E. tarda. Antigen uptake assay indicated PoMHC I alpha participated in cells antigen presentation. Collectively, this study is the first report that MHC I alpha plays an important role in immune defense against intracellular bacterial pathogen in teleost. Taken together, these findings add new insights into the biological function of teleost MI-IC I alpha and emphasize the importance of MHC I gene products for the control of E. tarda infection.