title: Epithelial control of the human pDC response to extracellular bacteria.
abstract: Plasmacytoid pre-dendritic cells (pDCs) are specialized in responding to nucleic acids, and link innate with adaptive immunity. Although the response of pDCs to viruses is well established, whether pDCs can respond to extracellular bacteria remains controversial. Here, we demonstrate that extracellular bacteria such as Neisseria meningitidis, Haemophilus influenzae, and Staphylococcus aureus activate pDCs to produce IFN-α, TNF-α, IL-6, and to upregulate CD86 expression. We observed that pDCs were present within tonsillar crypts and oro-nasopharyngeal epithelium, where they may contact extracellular bacteria, in situ. Tonsil epithelium-conditioned supernatants inhibited IFN-α, TNF-α, and IL-6 triggered by the direct contact of N. meningitidis or S. aureus with pDCs. However, pDC priming of naive T cells was not affected, suggesting that tonsil epithelium micro-environment limits local inflammation while preserving adaptive immunity in response to extracellular bacteria. Our results reveal an important and novel function of pDCs in the initiation of the mucosal innate and adaptive immunity to extracellular bacteria.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) U932, Paris, France.
authors: Paula
authors: P
authors: Michea
authors: Pablo
authors: P
authors: Vargas
authors: Marie-Hélène
authors: MH
authors: Donnadieu
authors: Mario
authors: M
authors: Rosemblatt
authors: María Rosa
authors: MR
authors: Bono
authors: Guillaume
authors: G
authors: Duménil
authors: Vassili
authors: V
authors: Soumelis
mesh_terms: D056704:Adaptive Immunity; D000234:Adenoids / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D002450:Cell Communication; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D006193:Haemophilus influenzae / Q000254:growth & development; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D009345:Neisseria meningitidis / Q000254:growth & development; D020545:Respiratory Mucosa / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D015854:Up-Regulation
chemical_list: D051940:B7-2 Antigen; C497964:CD86 protein, human; D017077:Culture Media, Conditioned; D016898:Interferon-alpha; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha