Adenoviral vectors stimulate innate immune responses in macrophages through cross-talk with epithelial cells

作者：Lee Benjamin H; Kushwah Rahul; Wu Jing; Ng Philip; Palaniyar Nades; Grinstein Sergio; Philpott Dana J; Hu Jim^*

来源：Immunology Letters, 2010, 134(1): 93-102.

DOI：10.1016/j.imlet.2010.09.003

• Adenovirus
• Innate immunity
• Macrophage
• Cell-cell interaction
• Gene therapy

Although adenovirus vectors (Ads) have been widely utilized for gene delivery their clinical application has been hampered by host immune responses It has been shown that macrophages can induce inflammatory response against Ads in vivo but they are not easily activated by Ads in vitro suggesting their activation requires interaction with other cells In this study we investigated the interaction between macrophages and epithelial cells during Ad infection Ad infection of the macrophage-epithelial cell co-culture resulted in rapid and drastic changes in the cell culture such as decrease in pH within 24h indicating macrophage activation Ad infected co-culture showed several characteristics of inflammation including cytotoxicity induction of pro-Inflammatory cytokines and generation of nitric oxide and reactive oxygen species These signs of macrophage activation and inflammation were observed exclusively in the co-culture and were absent or significantly weaker in the macrophage mono-culture suggesting that there was a synergistic response by the interaction between macrophages and epithelial cells We found that inhibition of NF-kappa B activation significantly reduced the inflammatory responses in the co-culture Furthermore we show that only the macrophages adjacent to epithelial cells w

• 出版日期2010-11-30
• 单位河北医科大学