TLR9型
先天免疫系统
生物
TLR7型
CD80
免疫学
CD86
免疫系统
树突状细胞
TLR3型
细胞因子
病毒载体
TLR4型
Toll样受体
CD40
细胞生物学
T细胞
基因表达
细胞毒性T细胞
生物化学
基因
DNA甲基化
体外
重组DNA
作者
Tomoko Yamaguchi,Kenji Kono,Noriko Koizumi,Fuminori Sakurai,Kazuko Nakashima,Haruna Sakurai,Tomomi Sasaki,Naoki Okada,Koichi Yamanishi,Hiroyuki Mizuguchi
出处
期刊:Human Gene Therapy
[Mary Ann Liebert]
日期:2007-08-01
卷期号:18 (8): 753-762
被引量:85
摘要
A replication-incompetent adenoviral (Ad) vector is generating interest for both gene therapy and immunotherapy. A major limitation of the use of Ad vectors is the innate immune response, which causes inflammatory cytokine production and tissue damage; however, the precise mechanism of the innate immune response remains to be clarified. Here, we show that serotype 5 human Ad vectors elicit innate immune responses through a myeloid differentiating factor 88 (MyD88)/Toll-like receptor (TLR)-9-dependent and/or -independent manner according to cell type. After stimulation with Ad vectors, the production of interleukin (IL)-6 and IL-12 was significantly decreased in MyD88- or TLR9-deficient dendritic cells (DCs), compared with wild-type DCs. In addition, the surface expression of maturation marker proteins, such as CD40, CD80, CD86, and MHC class II, in MyD88- or TLR9-deficient granulocyte-macrophage colony-stimulating factor (GM-CSF)-DCs was similar to that in wild-type DCs. On the other hand, MyD88- or TLR9-deficient peritoneal macrophages produced the same level of IL-6 as wild-type macrophages after infection with Ad vectors. We did not find any differences in the mRNA expression levels of the molecules involved in innate immunity, such as MyD88, TLR3, TLR7, and TLR9, between DCs and macrophages. The intravenous injection of luciferase-expressing Ad vectors into MyD88- or TLR9-deficient mice resulted in almost comparable levels of IL-6 and IL-12 production and luciferase expression with wild-type mice. These results suggest that Ad vectors can activate innate immunity via MyD88/TLR9-dependent and -independent mechanisms.
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