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Pubmed ID :29150602
Publication Date : //

TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells.


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.

Authors : Saitoh Shin-Ichiroh , Abe Fumiko , Kanno Atsuo , Tanimura Natsuko , Mori Saitoh Yoshiko , Fukui Ryutaro , Shibata Takuma , Sato Katsuaki , Ichinohe Takeshi , Hayashi Mayumi , Kubota Kazuishi , Kozuka-Hata Hiroko , Oyama Masaaki , Kikko Yorifumi , Katada Toshiaki , Kontani Kenji , Miyake Kensuke ,

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