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.

Previous studies have demonstrated impaired serum cytokine production and increased susceptibility to infection in 3d mice infected with a high lethal dose of MCMV [35] ; however, our study is the first report to document the contribution of the 3d mutation to impaired MCMV defense in the liver. In agreement with the study by Tabeta et al. [35] , our results, using a moderate dose of MCMV, demonstrated a diminished serum cytokine response (Fig. 1) , reduced splenic IFN-a production and elevated viral titers in the spleen (data not shown). These results were not unexpected given the known role for the nucleic acid-sensing TLRs in MCMV recognition and the subsequent production of proinflammatory cytokines and type I IFN by splenic pDCs [19, 31, 33, 44] . Production of type I IFN is a critical early step in antiviral defense, and we further demonstrated diminished levels of liver IFN-a in MCMV-infected 3d mice. This defect was in part due to an impaired ability of liver pDCs to express this cytokine and is consistent with previous reports identifying pDCs as an important early source of IFN-a in response to TLR7 and TLR9 ligands [10, 20, 31, 32, 33, [45] [46] [47] . Altogether, these results concur with previous studies indicating that pDCs are the predominant leukocyte producer of type I IFN in the liver during early MCMV infection [20] , and demonstrate that production of these cytokines by pDCs is influenced by the 3d mutation.