Baicalin Relieves Glaesserella parasuis-Triggered Immunosuppression Through Polarization via MIF/CD74 Signaling Pathway in Piglets

<i>Glaesserella parasuis</i> (<i>G. parasuis</i>) infection is responsible for Glässer's disease in pigs. <i>G. parasuis</i> could trigger piglet immunosuppression, but the mechanism of inducing immunosuppression by <i>G. parasuis</i> remains unknown. Macrophage migration inhibitory factor (MIF)/CD74 axis has been shown to participate in inflammation response and immunosuppression, but the function of MIF/CD74 during immunosuppression elicited by <i>G. parasuis</i> has not been fully explored. This experiment explored the efficacy of baicalin on immunosuppression elicited by <i>G. parasuis</i> alleviation through regulating polarization via the MIF/CD74 signaling pathway. Our data indicated that baicalin reduced IL-1β, IL-6, IL-8, IL-18, TNF-α, and COX-2 expression, and regulated MIF/CD74 axis expression in the spleen. Immunohistochemistry analysis showed that baicalin enhanced CD74 protein levels in the spleen of piglets induced by <i>G. parasuis</i>. Baicalin regulated the PI3K/Akt/mTOR signaling pathway and RAF/MEK/ERK signaling activation, modified the expression of the autophagy-related proteins Beclin-1, P62, and LC3B, promoted M2 polarization to M1 polarization, and enhanced CD3, CD4, CD8, and TIM3 levels in the spleen of piglets elicited by <i>G. parasuis</i>. Our study reveals the important functions of the MIF/CD74 axis in <i>G. parasuis</i>-induced immunosuppression and may offer a new therapeutic method to control <i>G. parasuis</i> infection.