title: Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection.
abstract: Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection.
authors.affiliation: Department of Genetics, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Blasius
authors.forename: Philippe
authors.initials: P
authors.lastname: Krebs
authors.forename: Brian M
authors.initials: BM
authors.lastname: Sullivan
authors.forename: Michael B
authors.initials: MB
authors.lastname: Oldstone
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Popkin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D051193:Toll-Like Receptors / Q000235:genetics; D014766:Viremia / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D026901:Membrane Transport Proteins; C554281:Slc15a4 protein, mouse; D051193:Toll-Like Receptors