Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction

Guo Yun Chen, Xi Chen, Samantha King, Karen A. Cavassani, Jiansong Cheng, Xincheng Zheng, Hongzhi Cao, Hai Yu, Jingyao Qu, Dexing Fang, Wei Wu, Xue Feng Bai, Jin Qing Liu, Shireen A. Woodiga, Chong Chen, Lei Sun, Cory M. Hogaboam, Steven L. Kunkel, Pan Zheng, Yang Liu

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Suppression of inflammation is critical for effective therapy of many infectious diseases. However, the high rates of mortality caused by sepsis attest to the need to better understand the basis of the inflammatory sequelae of sepsis and to develop new options for its treatment. In mice, inflammatory responses to host danger-associated molecular patterns (DAMPs), but not to microbial pathogen-associated molecular patterns (PAMPs), are repressed by the t interaction of CD24 and SiglecG (SIGLEC10 in human). Here we use an intestinal perforation model of sepsis to show that microbial sialidases target the sialic acid-based recognition of CD24 by SiglecG/10 to exacerbate inflammation. Sialidase inhibitors protect mice against sepsis by a mechanism involving both CD24 and Siglecg, whereas mutation of either gene exacerbates sepsis. Analysis of sialidase-deficient bacterial mutants confirms the key contribution of disrupting sialic acid-based pattern recognition to microbial virulence and supports the clinical potential of sialidase inhibition for dampening inflammation caused by infection.

Original languageEnglish (US)
Pages (from-to)428-435
Number of pages8
JournalNature Biotechnology
Volume29
Issue number5
DOIs
StatePublished - May 2011

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ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

Cite this

Chen, G. Y., Chen, X., King, S., Cavassani, K. A., Cheng, J., Zheng, X., Cao, H., Yu, H., Qu, J., Fang, D., Wu, W., Bai, X. F., Liu, J. Q., Woodiga, S. A., Chen, C., Sun, L., Hogaboam, C. M., Kunkel, S. L., Zheng, P., & Liu, Y. (2011). Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nature Biotechnology, 29(5), 428-435. https://doi.org/10.1038/nbt.1846