Effects Of Macrophage Migration Inhibitory Factor (MIF) In Fish Bacterial Sepsis

Over the last decades, MIF has emerged to be a multi-functional cytokine that played pivotal roles in variety of biological activities, especially in innate immunity, MIF was believed to be critical in the control of inflammatory responses 'set point' by regulating the release of other pro-inflammatory cytokines. In the present study, by establishment of A.hydrophila mediated zebrafish sepsis model, we investigated the functions of MIF in the bacterial sepsis. The result showed that MIF was up-regulated after bacterial infection, and a bolus of recombinant MIF could exacerbate sepsis induced by this infection, neutralization of the MIF activity with anti-MIF antibody could protect fish from septic shock, confirming the harmful effect of an excessive amount of MIF. Our study showed that MIF, TLR5a, TLR5b, TLR9, TLR20a, IL-1βand TNF-αwas induced after infection with A.hydrophila, the research of the relationship between those during sepsis demonstrated that MIF was released after bacterial infection, which induced the expressions of TLR5a, TLR5b, TLR9, TLR20a, these abundant of TLRs made the body in the state of highly sensitive to the bacterial, TLRs recognized the molecules called pathogen-associated molecular patterns(PAMPs) of the bacteria, activating the cascade of the inflammatory pathway, resulting in releasing of inflammatory factors such as IL-1βand TNF-α, and if overdose of which will causing septic shock. The results using Tetraodon MIF in zebrafish were nearly the same of that using zebrafish MIF in zebrafish, confirming the conservatism of MIF between fishes. We hope that our functional characterization of MIF in fish will not only enrich the knowledge of fish immunology, but will also contribute to a better cross-species understanding of the evolutionary history of the MIF family and MIF-mediated regulatory roles in inflammatory immunity. We also hope that it will provide an opportunity to develop a novel fish model for clinical investigations and medical applications of MIF based therapies...