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

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.

• Authors: 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
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 24 Issue 2 Pg. 249-260.e4 (08 08 2018) ISSN: 1934-6069 [Electronic] United States
• PMID: 30092201 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• CCR6 protein, mouse
• Cytokines
• Homeodomain Proteins
• Neuropeptides
• Receptors, CCR6
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Member 14
• Tnfsf14 protein, mouse
• Tumor Necrosis Factor Ligand Superfamily Member 14
• RAG-1 protein
• Interferon-gamma

Topics

• Adoptive Transfer
• Adult
• Animals
• Cytokines (metabolism)
• Disease Models, Animal
• Enterobacteriaceae Infections (pathology, prevention & control)
• Homeodomain Proteins (genetics, metabolism)
• Host-Pathogen Interactions (immunology, physiology)
• Humans
• Interferon-gamma (metabolism)
• Lymphocytes (immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neuropeptides (metabolism)
• Protein Transport
• Receptors, CCR6 (genetics, metabolism)
• Receptors, Tumor Necrosis Factor (metabolism)
• Receptors, Tumor Necrosis Factor, Member 14 (immunology, metabolism)
• Signal Transduction
• Spleen (microbiology, pathology)
• Tumor Necrosis Factor Ligand Superfamily Member 14 (metabolism)
• Yersinia enterocolitica (pathogenicity)