RRC ID 49606
Author Saitoh SI, Abe F, Kanno A, Tanimura N, Mori Saitoh Y, Fukui R, Shibata T, Sato K, Ichinohe T, Hayashi M, Kubota K, Kozuka-Hata H, Oyama M, Kikko Y, Katada T, Kontani K, Miyake K.
Title TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells.
Journal Nat Commun
Abstract 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.
Volume 8(1)
Pages 1592
Published 2017-11-17
DOI 10.1038/s41467-017-01687-x
PII 10.1038/s41467-017-01687-x
PMID 29150602
PMC PMC5693993
MeSH Animals Cells, Cultured Dendritic Cells / immunology* Dendritic Cells / metabolism Integrins / immunology Integrins / metabolism Interferon Type I / immunology* Interferon Type I / metabolism Mechanistic Target of Rapamycin Complex 1 / immunology Mechanistic Target of Rapamycin Complex 1 / metabolism Membrane Glycoproteins / genetics Membrane Glycoproteins / immunology* Membrane Glycoproteins / metabolism Mice, Inbred C57BL Mice, Knockout Microtubules / immunology Microtubules / metabolism RNA, Viral / immunology* Signal Transduction / immunology TNF Receptor-Associated Factor 3 / immunology TNF Receptor-Associated Factor 3 / metabolism TNF Receptor-Associated Factor 6 / immunology TNF Receptor-Associated Factor 6 / metabolism Toll-Like Receptor 7 / genetics Toll-Like Receptor 7 / immunology* Toll-Like Receptor 7 / metabolism
IF 12.121
Times Cited 23
Mice RBRC00850