title: Plasmacytoid dendritic cell-derived IFNα modulates Th17 differentiation during early Bordetella pertussis infection in mice.
abstract: Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). T helper 17 (Th17) cells have a central role in the resolution of the infection. Emerging studies document that type I interferons (IFNs) suppress Th17 differentiation and interleukin (IL)-17 responses in models of infection and chronic inflammation. As plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs, we hypothesize that during B. pertussis infection in mice, pDC-derived IFNα inhibits a rapid increase in Th17 cells. We found that IFNα-secreting pDCs appear in the lungs during the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection or later. The presence of IFNα led to reduced Th17 differentiation and proliferation in vitro. Furthermore, in vivo blocking of IFNα produced by pDCs during infection with B. pertussis infection resulted in early increase of Th17 frequency, inflammation, and reduced bacterial loads in the airways of infected mice. Taken together, the experiments reported here describe an inhibitory role for pDCs and pDC-derived IFNα in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough.
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: V
authors.initials: V
authors.lastname: Wu
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Smith
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: H
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Nguyen
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ferguson
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: P
authors.initials: P
authors.lastname: Llontop
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Youngman
authors.affiliation: Department of Biology, San José State University, San José, California, USA.
authors.forename: T
authors.initials: T
authors.lastname: Abramson
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D058491:Bacterial Load; D001886:Bordetella pertussis / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D056747:Immunomodulation; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D058504:Th17 Cells / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D016898:Interferon-alpha