Peyer's patch-involved gut microbiota facilitates anti-HBV immunity in mice

派尔集合淋巴结相关肠道菌群促进小鼠产生抗乙肝病毒免疫力

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作者:Yifan Li, Shihong Zhong, Zihan Jin, Guofu Ye, Tianling Zhang, Zhipeng Liu, Zhenguo Liu, Zhaofeng Zeng, Qiong Li, Yuhao Wang, Yanda Zhao, Libo Tang, Huaihong Chen, Yongyin Li

Background

Gut microbiota is crucial for immune homeostasis and is associated with the prognosis of chronic hepatitis B infection. Peyer's patches (PPs), characterized by intestinal mucosa localization, are involved in the gut microbiota-mediated immune response. However, whether and how PPs orchestrate gut microbiota-modulated anti-hepatitis B virus (HBV) response remain elusive. This study aims to elucidate the role of PPs in gut microbiota-mediated anti-HBV adaptive immunity.

Conclusion

PPs orchestrate gut microbiota-mediated intrahepatic anti-HBV cellular immunity, underlining the significance of remote manipulating the "gut microbiota-PPs" axis for achieving optimum anti-HBV response.

Methods

We investigated the effects of gut microbiota and PPs on adaptive immune responses by transcriptomic, phenotypic, and functional analyzes from an HBV mouse model with gut commensal microbiota and PP-depleting interventions.

Results

Depletion of gut microbiota impaired systemic adaptive immune responses, resulting in a delayed HBV antigen clearance. Differentially expressed genes analysis of PPs revealed that pathways related to adaptive immune responses were significantly downregulated in gut microbiota-deficient mice. Notably, the depletion of PPs could abolish gut microbiota-boosted intrahepatic HBV-specific T cell response, leading to a higher serum hepatitis B surface antigen level in mice.

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