Identification of Macrophage Migration Inhibitory Factor in Mytilus coruscus and Its Role in Methylation During Antibacterial Immunity

Macrophage migration inhibitory factor (MIF) is broadly acknowledged as a central pro-inflammatory regulator, owing to its multifaceted functions including immune cell recruitment, initiation and amplification of pro-inflammatory cytokine cascades, enhancement of macrophage viability, facilitation of macrophage polarization toward a pro-inflammatory state, and attenuation of glucocorticoid-mediated immunosuppression. However, functional investigations of MIF in Mytilus coruscus remain limited. In this study, we identified the MIF gene in M. coruscus, and bioinformatic analyses revealed that the gene encodes a 115-amino-acid polypeptide that exhibits close phylogenetic affinity with MIF homologs from other mollusks. McMIF was predominantly expressed in immune-related tissues, with notably high expression levels in the digestive gland. Upon Vibrio alginolyticus infection, both the mRNA and protein levels of McMIF were significantly upregulated, suggesting that McMIF is involved in the antibacterial immune response of M. coruscus. Meanwhile, the m6A modification level of McMIF was markedly reduced following infection, suggesting a potential relationship between m6A modification and the antibacterial immune function of MIF. Furthermore, knockdown of McMIF followed by LPS stimulation led to an increased level of apoptosis in digestive gland cells, suggesting that McMIF is involved in the inhibition of apoptosis induced by immune stimulation. Collectively, these findings provide insights into the immunological characteristics of McMIF in M. coruscus.