Preprint / Version 1

Antibody efficacy in bacterial sepsis is rescued by targeting macrophage PAMP-STAT1-FcRn axis

This article is a preprint and has not been certified by peer review.

Authors

    Xinyu Wei,  
    Xinyu Wei
    Xiaoxia Su,  
    Xiaoxia Su
    Qianyu Duan,  
    Qianyu Duan
    Miao Pei,  
    Miao Pei
    Qun Huang,  
    Qun Huang
    Xuan Lai,  
    Xuan Lai
    Jiani Zhang,  
    Jiani Zhang
    Danzhi Wu,  
    Danzhi Wu
    Beibei Chen,  
    Beibei Chen
    Yu Deng,  
    Yu Deng
    Ying Huang,  
    Ying Huang
    Jinzhou Ye,  
    Jinzhou Ye
    Teng Zhang,  
    Teng Zhang
    Hua Zhou,  
    Hua Zhou
    • the Second Affiliated Hospital Zhejiang University
    Xiaoting Hua,  
    Xiaoting Hua
    • Sir Run Run Shaw Hospital image/svg+xml
    • Zhejiang Provincial Engineering Research Center of Innovative Instruments for Precise Pathogen Detection
    Xin Ding,  
    Xin Ding
    • Shenzhen Campus of Sun Yat-sen University
    Mao Li,  
    Mao Li
    Xianjie Liu,  
    Xianjie Liu
    • Shenzhen International Institute for Biomedical Research
    Wenjun Chen,  
    Wenjun Chen
    Xinhai Chen
    Xinhai Chen
    • Shenzhen Bay Laboratory image/svg+xml
    • Shenzhen Medical Academy of Research and Translation image/svg+xml
    • Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation
Categories
Immunology & Microbiology
Keywords
IgG; Bacterial sepsis; Macrophage; FcRn; STAT1

Abstract

Sepsis induces a significant loss of circulating IgG, but the underlying mechanism has remained obscure. Here, we identify a previously unrecognized pathogenic axis that directly links bacterial PAMPs to antibody failure. During bacterial sepsis, LPS and PGN potently activate macrophage STAT1, which in turn transcriptionally silences FcRn, collapsing IgG salvage pathways and driving rapid antibody catabolism. This IgG-destabilizing mechanism is strikingly macrophage-specific in the mouse liver and spleen and is conserved in human macrophages. Loss of macrophage FcRn ablates the antibody protection, whereas inhibition of Toll-like receptor 4 (TLR4) or STAT1 signaling potently enhances antibody efficacy in septic mice. These findings uncover a fundamental mechanism of sepsis-induced immunosuppression and reveal a tractable intervention point for rescuing antibody therapeutics against bacterial sepsis.

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DOI:

https://doi.org/10.65215/LTSpreprints.2026.02.12.000130

Submission ID:

130

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Posted

2026-02-13

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How to Cite

Wei, X., Su, X., Duan, Q., Pei, M., Huang, Q., Lai, X., Zhang, J., Wu, D., Chen, B., Deng, Y., Huang, Y., Ye, J., Zhang, T., Zhou, H., Hua, X., Ding, X., Li, M., Liu, X., Chen, W., & Chen, X. (2026). Antibody efficacy in bacterial sepsis is rescued by targeting macrophage PAMP-STAT1-FcRn axis. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.02.12.000130

Declaration of Competing Interests

The authors declare no competing interests to disclose.

Copyright

The copyright holder for this preprint is the author/funder.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.