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Functional vulnerability of liver macrophages to capsules defines virulence of blood-borne bacteria

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posted on 2022-07-01, 10:50 authored by H An, C Qian, Y Huang, J Li, X Tian, J Feng, J Hu, Y Fang, F Jiao, Y Zeng, X Huang, X Meng, X Liu, X Lin, Z Zeng, M Guilliams, A Beschin, Y Chen, Y Wu, J Wang, MR Oggioni, J Leong, JW Veening, H Deng, R Zhang, H Wang, J Wu, Y Cui, JR Zhang
Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo infection conditions. Here we show that the capsules primarily target the liver to enhance bacterial survival at the onset of blood-borne infections. In a mouse sepsis model, the capsules enabled human pathogens Streptococcus pneumoniae and Escherichia coli to circumvent the recognition of liver-resident macrophage Kupffer cells (KCs) in a capsular serotype-dependent manner. In contrast to effective capture of acapsular bacteria by KCs, the encapsulated bacteria are partially (low-virulence types) or completely (high-virulence types) "untouchable" for KCs. We finally identified the asialoglycoprotein receptor (ASGR) as the first known capsule receptor on KCs to recognize the low-virulence serotype-7F and -14 pneumococcal capsules. Our data identify the molecular interplay between the capsules and KCs as a master controller of the fate and virulence of encapsulated bacteria, and suggest that the interplay is targetable for therapeutic control of septic infections.

Funding

This work was supported by grants from National Natural Science Foundation of China to J.-R. Zhang (31820103001 and 31530082), Tsinghua University Spring Breeze Fund to J.-R. Zhang (20201080767), and the Tsinghua-Peking Joint Center for Life Sciences Postdoctoral Foundation and the China Postdoctoral Science Foundation to H. An (2016M590085).

History

Citation

An, Haoran, et al. "Functional vulnerability of liver macrophages to capsules defines virulence of blood-borne bacteria." Journal of Experimental Medicine 219.4 (2022): e20212032.

Author affiliation

Department of Genetics and Genome Biology

Version

  • VoR (Version of Record)

Published in

The Journal of Experimental Medicine

Volume

219

Issue

4

Pagination

e20212032

Publisher

Rockefeller University Press

issn

0022-1007

eissn

1540-9538

Acceptance date

2022-01-24

Copyright date

2021

Available date

2022-03-08

Language

eng

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