Human metapneumovirus glycoprotein G inhibits TLR4-dependent signaling in monocyte-derived dendritic cells.
Human metapneumovirus glycoprotein G inhibits TLR4-dependent signaling in monocyte-derived dendritic cells.
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DOI：
10.4049/jimmunol.1002589
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Casola A
中科院分区：
文献类型：
--
作者：
Kolli D;Bao X;Liu T;Hong C;Wang T;Garofalo RP;Casola A
Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory infections in children and adults. Recent work from our group demonstrated that hMPV G glycoprotein is an important virulence factor, responsible for inhibiting innate immune responses in airway epithelial cells. Myeloid dendritic cells are potent antigen presenting cells and play a major role in initiating and modulating the innate and adaptive immune responses. In this study, we found that TLR4 plays a major role in hMPV-induced activation of monocyte-derived dendritic cells (moDCs), as downregulation of its expression by siRNA significantly blocked hMPV-induced chemokine and type I interferon expression. Similar results were found in bone marrow derived-dendritic cells (BM-DCs) from TLR4 deficient mice. MoDCs infected with a virus lacking G protein expression (rhMPV-ΔG) produced higher levels of cytokines and chemokines, compared to cells infected with wild-type virus (rhMPV-WT), suggesting that G protein plays an inhibitory role in viral-induced cellular responses. Specifically, G protein affects TLR4-dependent signaling, as rhMPV-ΔG infection of moDCs inhibited LPS-induced production of cytokine and chemokines significantly less than rhMPV-WT, and treatment of moDCs with purified G protein resulted in a similar inhibition of LPS-dependent signaling. Our results demonstrate that hMPV G protein plays an important role in inhibiting host innate immune responses, likely affecting adaptive responses too.
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DOI：
10.1016/s0140-6736(02)11391-2
发表时间：
2002-11-02
期刊：
Lancet (London, England)
影响因子：
--
作者：
Jartti T;van den Hoogen B;Garofalo RP;Osterhaus AD;Ruuskanen O
通讯作者：
Ruuskanen O
人元病毒糖蛋白G抑制先天免疫反应。
影响因子：
6.7
作者：
Bao, Xiaoyong;Liu, Tianshuang;Shan, Yichu;Li, Kui;Garofalo, Roberto P.;Casola, Antonella
通讯作者：
Casola, Antonella
影响因子：
5.4
作者：
Liu, Ping;Jamaluddin, Mohammad;Brasier, Allan R.
通讯作者：
Brasier, Allan R.
影响因子：
5.4
作者：
Ehl, S;Bischoff, R;Freudenberg, M
通讯作者：
Freudenberg, M
影响因子：
3.2
作者：
Lizundia, Reoina;Sauter, Kav-Sara;Werling, Dirk
通讯作者：
Werling, Dirk