title: Pivotal role of plasmacytoid dendritic cells in inflammation and NK-cell responses after TLR9 triggering in mice.
abstract: The physiologic role played by plasmacytoid dendritic cells (pDCs) in the induction of innate responses and inflammation in response to pathogen signaling is not well understood. Here, we describe a new mouse model lacking pDCs and establish that pDCs are essential for the in vivo induction of NK-cell activity in response to Toll-like receptor 9 (TLR9) triggering. Furthermore, we provide the first evidence that pDCs are critical for the systemic production of a wide variety of chemokines in response to TLR9 activation. Consequently, we observed a profound alteration in monocyte, macrophage, neutrophil, and NK-cell recruitment at the site of inflammation in the absence of pDCs in response to CpG-Dotap and stimulation by microbial pathogens, such as Leishmania major, Escherichia coli, and Mycobacterium bovis. This study, which is based on the development of a constitutively pDC-deficient mouse model, highlights the pivotal role played by pDCs in the induction of innate immune responses and inflammation after TLR9 triggering.
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Département d'Immunologie, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Guillerey
authors.forename: Juliette
authors.initials: J
authors.lastname: Mouriès
authors.forename: Giulia
authors.initials: G
authors.lastname: Polo
authors.forename: Noelle
authors.initials: N
authors.lastname: Doyen
authors.forename: Helen K W
authors.initials: HK
authors.lastname: Law
authors.forename: Susan
authors.initials: S
authors.lastname: Chan
authors.forename: Philippe
authors.initials: P
authors.lastname: Kastner
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.forename: Gilles
authors.initials: G
authors.lastname: Dadaglio
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007239:Infections / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000382:microbiology*; D018320:Leishmania major / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9