LIGHT-HVEM Signaling in Group3 Innate Lymphoid Cells Protects Against Enteric Bacterial Infection

Abstract

Abstract Innate lymphoid cells (ILC) are important regulators of early infection at mucosal barriers. They are known to be activated by cytokines and neuropeptides, but it remains to be determined if they integrate other signals in providing protection. The herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily, is expressed by all intestinal ILC subsets. Here, we show that HVEM signaling of ILC3 is important for host defense against oral infection with the enteric bacterial pathogen Yersinia enterocolitica (Y. enterocolitica). Surprisingly, IFNγ production by CCR6 negative ILC3 was strongly implicated in protection, likely because these cells were more numerous than other innate lymphocytes that produced IFNγ early after infection. We identified the TNF superfamily member LIGHT, as the ligand inducing HVEM signals in ILC. Therefore, our results demonstrate a novel role for LIGHT-HVEM signaling in regulating ILC3 IFNγ production and protection following infection.