Interferon-α Production by Plasmacytoid Dendritic Cells Is Dispensable for an Effective Anti-Cytomegalovirus Response in Adaptor Protein-3-Deficient Mice. [Del Prete A.*, Luganini A.* co-first author]

Adaptor protein-3 (AP-3) is a hetero-tetrameric complex, which regulates vesicular trafficking. Mutations of the β3A subunit cause the Hermansky-Pudlak syndrome type 2 (HPS-2), a rare genetic disease characterized by albinism, platelet defects and recurrent infections. Likewise, pearl mice, which lack functional AP-3, show several HPS-2 defects. AP-3 absence results in defective TLR trafficking and signalling in dendritic cells (DC), but its effect on the efficiency of the in vivo antiviral response is unclear. We evaluated the impact of AP-3 deficiency on the distribution of DC subsets, IFN production, and the susceptibility to murine cytomegalovirus (MCMV) infection. Pearl mice showed a distribution and frequency of conventional (cDC) and plasmacytoid DC (pDC) similar to that of wt mice both before and after MCMV infection. Moreover, pearl mice controlled MCMV infection even at high virus doses and showed a normal production of IFN-alpha Since pDC, but not cDC, from pearl mice showed an impaired IFN-alpha and TNF-alpha production in response to prototypic DNA (MCMV and HSV) or RNA (VSV) viruses in vitro, it is likely that MCMV infection can be controlled in vivo independently of an efficient production of IFN-alpha by pDC, and that AP-3 complex has a minimal impact on protective antiviral responses.