title: Interferon-α production by plasmacytoid dendritic cells is dispensable for an effective anti-cytomegalovirus response in adaptor protein-3-deficient mice.
abstract: Adaptor protein-3 (AP-3) is a heterotetrameric 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. The AP-3 absence results in defective toll-like receptor trafficking and signaling 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, interferon (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 wild-type 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-α. Since pDC, but not cDC, from pearl mice showed an impaired IFN-α and tumor necrosis factor-α production in response to prototypic DNA (MCMV and Herpes Simplex virus) or RNA (Vesicular Stomatitis virus) viruses in vitro, it is likely that MCMV infection can be controlled in vivo independently of an efficient production of IFN-α by pDC, and that the AP-3 complex has a minimal impact on protective antiviral responses.
authors.affiliation: 1 Department of Molecular and Translational Medicine, University of Brescia , Brescia, Italy .
authors.forename: Annalisa
authors.initials: A
authors.lastname: Del Prete
authors.forename: Anna
authors.initials: A
authors.lastname: Luganini
authors.forename: Sara
authors.initials: S
authors.lastname: Scutera
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.forename: Achille
authors.initials: A
authors.lastname: Anselmo
authors.forename: Deborah
authors.initials: D
authors.lastname: Greco
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gribaudo
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006801:Humans; D007109:Immunity; D016898:Interferon-alpha / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D033963:Adaptor Protein Complex 3; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha