The interception of blood-borne bacteria in the liver defines the outcomes of invasive bacterial infections, but the mechanisms of this antibacterial immunity are not fully understood. This study shows that natural antibodies (nAbs) to capsules enable liver macrophage Kupffer cells (KCs) to rapidly capture and kill blood-borne encapsulated bacteria in mice. Affinity pulldown with serotype-10A capsular polysaccharides (CPS10A) of Streptococcus pneumoniae (Spn10A) led to the identification of CPS10A-binding nAbs in serum. The CPS10A–antibody interaction enabled KCs to capture Spn10A bacteria from the bloodstream, in part through complement receptors on KCs. The nAbs were found to recognize the β1-6-linked galactose branch of CPS10A and similar moieties of serotype-39 S. pneumoniae and serotype-K50 Klebsiella pneumoniae capsules. More importantly, the nAbs empowered KCs to capture serotype-39 S. pneumoniae and serotype-K50 K. pneumoniae in the liver. Collectively, our data have revealed a highly effective immune function of nAb against encapsulated bacteria and emphasize the concept of treating septic encapsulated bacterial diseases with monoclonal antibodies.
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December 24 2024
Natural antibodies to polysaccharide capsules enable Kupffer cells to capture invading bacteria in the liver sinusoids
Xianbin Tian
,
Xianbin Tian
*
(Conceptualization, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
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Yanni Liu
,
Yanni Liu
*
(Formal analysis, Project administration)
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
2
Tsinghua-Peking Center for Life Sciences, Tsinghua University
, Beijing, China
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Kun Zhu
,
Kun Zhu
(Methodology)
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
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Haoran An
,
Haoran An
(Formal analysis, Methodology, Validation)
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
3
Institute of Medical Technology, Peking University Health Science Center
, Beijing, China
4Department of Microbiology and Infectious Disease Center,
Peking University Health Science Center
, Beijing, China
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Jie Feng
,
Jie Feng
(Resources)
5State Key Laboratory of Microbial Resources,
Institute of Microbiology, Chinese Academy of Sciences
, Beijing, China
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Linqi Zhang
,
Linqi Zhang
(Conceptualization, Formal analysis, Investigation, Resources, Supervision, Writing - review & editing)
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
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Jing-Ren Zhang
(Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing)
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
Correspondence to Jing-Ren Zhang: [email protected]
Search for other works by this author on:
Xianbin Tian
Conceptualization, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing
*
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
2
Tsinghua-Peking Center for Life Sciences, Tsinghua University
, Beijing, China
Kun Zhu
Methodology
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
Haoran An
Formal analysis, Methodology, Validation
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
3
Institute of Medical Technology, Peking University Health Science Center
, Beijing, China
4Department of Microbiology and Infectious Disease Center,
Peking University Health Science Center
, Beijing, China
Jie Feng
Resources
5State Key Laboratory of Microbial Resources,
Institute of Microbiology, Chinese Academy of Sciences
, Beijing, China
Linqi Zhang
Conceptualization, Formal analysis, Investigation, Resources, Supervision, Writing - review & editing
1
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University
, Beijing, China
Correspondence to Jing-Ren Zhang: [email protected]
*
X. Tian and Y. Liu contributed equally to this paper.
Disclosures: The authors declare no competing interests exist.
Received:
April 25 2024
Revision Received:
September 23 2024
Accepted:
November 25 2024
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funder(s):
National Key Research and Development Program of China
- Award Id(s): 2023YFc2306301
Funder(s):
National Natural Science Foundation of China
- Award Id(s): 82330071
Funder(s):
Tsinghua University Initiative Scientific Research Program
- Award Id(s): 20243080033
© 2024 Tian et al.
2024
Tian et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
This work is licensed under a
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
.
J Exp Med (2025) 222 (2): e20240735.
Article history
Received:
April 25 2024
Revision Received:
September 23 2024
Accepted:
November 25 2024
Citation
Xianbin Tian, Yanni Liu, Kun Zhu, Haoran An, Jie Feng, Linqi Zhang, Jing-Ren Zhang; Natural antibodies to polysaccharide capsules enable Kupffer cells to capture invading bacteria in the liver sinusoids. J Exp Med 3 February 2025; 222 (2): e20240735. doi: https://doi.org/10.1084/jem.20240735
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