UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection

Crane, Meredith J.; Gaddi, Pamela J.; Salazar-Mather, Thais P.

The innate immune response is important both in establishing early control of virus replication and in coordinating downstream adaptive responses. Following MCMV infection, virus-specific CD8+ T cells are recruited to the liver within 5 days and control viral replication at this site through release of cytotoxic molecules and production of cytokines such as IFN-c and TNF-a [26, 27] . Given the abated liver cytokine responses observed in 3d mice, the effect of endosomal TLR signaling on liver CD8+ T cell responses was examined at late time points during acute MCMV infection. The results shown in Fig. 3A demonstrate comparable absolute numbers of CD8+ T cells in WT and 3d mice at days 5 and 7 post-MCMV infection, a trend that was also reflected in proportion (data not shown). To determine whether CD8+ T cells in 3d mice were properly activated against MCMV infection, intracellular expression of IFN-c and TNF-a in CD8+ T cells was examined following ex vivo restimulation with H-2D b M45 viral peptide, an immunodominant epitope of MCMV [29] . CD8+ T cells from 3d mice expressed these two cytokines at day 5 and day 7 post-MCMV infection by proportion and absolute numbers at levels that were comparable or slightly increased over WT (Fig. 3 , B-E).