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

Glaesserella parasuis (G. parasuis) infection is responsible for Glässer's disease in pigs. G. parasuis could trigger piglet immunosuppression, but the mechanism of inducing immunosuppression by G. parasuis 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 G. parasuis has not been fully explored. This experiment explored the efficacy of baicalin on immunosuppression elicited by G. parasuis 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 G. parasuis. 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 G. parasuis. Our study reveals the important functions of the MIF/CD74 axis in G. parasuis-induced immunosuppression and may offer a new therapeutic method to control G. parasuis infection.