Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1

Guo Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha van de Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu

Research output: Contribution to journalArticle

Abstract

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced disruption of TLR4:Siglec E/F interactions. Absence of Neu1 in hematopoietic cells or systematic treatment with sialidase inhibitor Neu5Gc2en protected mice against endotoxemia. Our data raised an intriguing possibility of a broad repression of TLR function by Siglecs and a sialidase-mediated de-repression that allows positive feedback of TLR activation during infection.

Original languageEnglish (US)
Pages (from-to)e04066
JournaleLife
Volume3
DOIs
StatePublished - 2014

Keywords

  • E. coli
  • immunology
  • mouse
  • sialidase
  • Siglec
  • toll-like receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Chen, G. Y., Brown, N. K., Wu, W., Khedri, Z., Yu, H., Chen, X., van de Vlekkert, D., D'Azzo, A., Zheng, P., & Liu, Y. (2014). Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1. eLife, 3, e04066. https://doi.org/10.7554/eLife.04066