TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells
| Autor: | Mayumi Hayashi, Kensuke Miyake, Toshiaki Katada, Shin-ichiroh Saitoh, Atsuo Kanno, Kazuishi Kubota, Fumiko Abe, Ryutaro Fukui, Natsuko Tanimura, Katsuaki Sato, Yorifumi Kikko, Hiroko Kozuka-Hata, Masaaki Oyama, Yoshiko Mori Saitoh, Takeshi Ichinohe, Kenji Kontani, Takuma Shibata |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell signaling Integrins Endosome Science General Physics and Astronomy macromolecular substances Mechanistic Target of Rapamycin Complex 1 Microtubules General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Interferon medicine Animals Cell adhesion lcsh:Science Cells Cultured Mice Knockout TNF Receptor-Associated Factor 6 Multidisciplinary Membrane Glycoproteins TNF Receptor-Associated Factor 3 Effector Chemistry virus diseases hemic and immune systems General Chemistry TLR7 Dendritic Cells Type I interferon production Virology Cell biology Mice Inbred C57BL 030104 developmental biology Toll-Like Receptor 7 Type I interferon secretion Interferon Type I RNA Viral lcsh:Q 030215 immunology medicine.drug Signal Transduction |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC–pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7+ lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7. The type I interferon signaling molecules TRAF3, IKKα, and mTORC1 are constitutively associated in pDCs. TLR7 localizes to mTORC1 and induces association of TRAF3 with the upstream molecule TRAF6. Finally, type I interferons are secreted in the vicinity of cell–cell contacts between clustered pDCs. These results suggest that TLR7 needs to move to the cell periphery to induce robust type I interferon responses in pDCs. Antiviral immune responses involve clustering of plasmacytoid dendritic cells (pDC) in response to endosomal TLR7-mediated sensing of viral RNA. Here the authors show the GTPase Arl8b controls translocation of TLR7+ endosomes to the periphery of the cell via microtubule interactions, thus enabling pDC clustering and type I interferon production. |
| Databáze: | OpenAIRE |
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