LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric Bacterial Infection

Goo Young Seo, Jr Wen Shui, Daisuke Takahashi, Christina Song, Qingyang Wang, Kenneth Kim, Zbigniew Mikulski, Shilpi Chandra, Daniel A. Giles, Sonja Zahner, Pyeung Hyeun Kim, Hilde Cheroutre, Marco Colonna, Mitchell Kronenberg

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Innate lymphoid cells (ILCs) are important regulators of early infection at mucosal barriers. ILCs are divided into three groups based on expression profiles, and are activated by cytokines and neuropeptides. Yet, it remains unknown if ILCs integrate other signals in providing protection. We show that signaling through herpes virus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor superfamily, in ILC3 is important for host defense against oral infection with the bacterial pathogen Yersinia enterocolitica. HVEM stimulates protective interferon-γ (IFN-γ) secretion from ILCs, and mice with HVEM-deficient ILC3 exhibit reduced IFN-γ production, higher bacterial burdens and increased mortality. In addition, IFN-γ production is critical as adoptive transfer of wild-type but not IFN-γ-deficient ILC3 can restore protection to mice lacking ILCs. We identify the TNF superfamily member, LIGHT, as the ligand inducing HVEM signals in ILCs. Thus HVEM signaling mediated by LIGHT plays a critical role in regulating ILC3-derived IFN-γ production for protection following infection. Video Abstract:[Figure presented] Seo et al. find that IFN-γ-producing ILC3 in the small intestine are required for host protection against Yersinia enterocolitica infection. HVEM signaling in ILC3, mediated by the ligand LIGHT, is critical for regulating IFN-γ production for protection following infection.

Original languageEnglish
Pages (from-to)249-260.e4
JournalCell Host and Microbe
Volume24
Issue number2
DOIs
StatePublished - Aug 8 2018

Keywords

  • CCR6
  • HVEM
  • IFN-γ
  • LIGHT
  • Yersinia enterocolitica
  • ileum
  • infection
  • innate lymphoid cells

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    Seo, G. Y., Shui, J. W., Takahashi, D., Song, C., Wang, Q., Kim, K., Mikulski, Z., Chandra, S., Giles, D. A., Zahner, S., Kim, P. H., Cheroutre, H., Colonna, M., & Kronenberg, M. (2018). LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric Bacterial Infection. Cell Host and Microbe, 24(2), 249-260.e4. https://doi.org/10.1016/j.chom.2018.07.008