# Baicalin Alleviates Piglet Immunosuppression Induced by Glaesserella parasuis via Promoting CD163/Tumor Necrosis Factor-like Weak Inducer of Apoptosis-Mediated Autophagy

## TL;DR

Baicalin helps reduce piglet immunosuppression caused by Glaesserella parasuis by promoting autophagy through the CD163/TWEAK pathway.

## Contribution

This study reveals a novel mechanism by which baicalin alleviates G. parasuis-induced immunosuppression via CD163/TWEAK-mediated autophagy.

## Key findings

- Baicalin reduces cytokine production and alleviates vascular tissue damage in infected piglets.
- Baicalin promotes autophagy and inhibits NLRP3/Caspase 1 and Notch/Wnt signaling pathways.
- CD163 is differentially expressed in blood vessels of G. parasuis-challenged piglets.

## Abstract

Glaesserella parasuis (G. parasuis) causes vascular inflammation in piglets, resulting in vascular damage. However, the mechanism causing vascular inflammation remains unclear. Baicalin possesses an anti-inflammatory function. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been implicated in immunosuppression. CD163, a scavenger receptor expressed on macrophages that acts as a decoy receptor for TWEAK, plays a crucial role in the regulation of autophagy and inflammation. This research investigated the efficacy of baicalin in reducing immunosuppression elicited by G. parasuis through the regulation of CD163/TWEAK-mediated autophagy. The data demonstrated that G. parasuis altered routine blood indicators and biochemical parameters, increased cytokine production, and induced blood vessel tissue damage. G. parasuis reduced the CD3+ T cell proportion, CD3+CD4+ T cell proportion, and CD3+CD8+ T cell proportion in piglet blood. The proteomic analysis revealed that CD163 was differentially expressed in the blood vessels of challenged piglets. Baicalin was found to regulate CD163/TWEAK axis expression, inhibit Notch/Wnt signaling pathway activation, promote autophagy, and reduce NLRP3/Caspase 1 signaling pathway activation. Baicalin also decreased cytokine production and alleviated pathological tissue damage in the blood vessels of G. parasuis-challenged piglets. Taken together, this study indicates that baicalin alleviates G. parasuis-induced immunosuppression and might promote CD163/TWEAK-mediated autophagy. This finding suggests that baicalin could serve as a potential therapeutic agent to control G. parasuis infection and related vascular inflammation.