TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells.
TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells.
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DOI:
10.1038/s41467-017-01687-x
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发表时间:
2017-11-17
影响因子:
16.6
通讯作者:
Miyake K
中科院分区:
文献类型:
--
作者:
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
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.
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DOI:
10.1084/jem.20060401
发表时间:
2006-08-07
期刊:
The Journal of experimental medicine
影响因子:
--
作者:
Guiducci C;Ott G;Chan JH;Damon E;Calacsan C;Matray T;Lee KD;Coffman RL;Barrat FJ
通讯作者:
Barrat FJ
影响因子:
3.3
作者:
Nakae I;Fujino T;Kobayashi T;Sasaki A;Kikko Y;Fukuyama M;Gengyo-Ando K;Mitani S;Kontani K;Katada T
通讯作者:
Katada T
影响因子:
15.3
作者:
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者:
Garrone, P
影响因子:
30.5
作者:
通讯作者:
--
影响因子:
4.4
作者:
Hagberg, Niklas;Berggren, Olof;Ronnblom, Lars
通讯作者:
Ronnblom, Lars