Herpes virus entry mediator licenses Listeria infection induced immunopathology through control of type I interferon.

Apoptosis of the splenic lymphocytes is often induced during the acute phase of Listeria infection in mice. However, the underlying mechanism remains incompletely understood. Here, we found that herpes virus entry mediator (HVEM) plays an important role for Listeria infection induced lymphocyte apoptosis. Mechanistically, HVEM is not directly involved in listeriolysin O (LLO) induced lymphocyte apoptosis or interferon beta induced T cell activation per se. Interestingly, HVEM is partially required for Listeria induced interferon (IFN)-I production in the spleen, particularly in macrophages. Consequently, the bystander activation of lymphocytes is significantly lower in HVEM deficient mice than that in wild-type (WT) mice upon Listeria infection. Thus, our results have revealed a novel role of HVEM on the regulation of IFN-I and immunopathology during Listeria infection.