科研之友
微信
新浪微博
Facebook
分享链接
摘要
Aflatoxin B-1 (AFB(1)), which alters immune responses to mammals, is one of the most common mycotoxins in feeds and food. Swine influenza virus (SIV) is a major pathogen of both animals and humans. However, there have been few studies about the relationship between AFB1 exposure and SIV replication. Here, for the first time, we investigated the involvement of AFB1 in SIV replication in vitro and in vivo and explored the underlying mechanism using multiple cell lines and mouse models. In vitro studies demonstrated that low concentrations of AFB1 (0.01-0.25 mu g/ml) markedly promoted SIV replication as revealed by increased viral titers and matrix protein (M) mRNA and nucleoprotein (NP) levels in MDCK cells, A549 cells and PAMs. In vivo studies showed that 10-40 mu g/kg of AFB1 exacerbated SIV infection in mice as illustrated by significantly higher lung virus titers, viral M mRNA levels, NP levels, lung indexes and more severe lung damage. Further study showed that AFB(1) upregulated TLR4, but not other TLRs, in SIV-infected PAMs. Moreover, AFB(1) activated TLR4 signaling as demonstrated by the increases of phosphorylated NF kappa B p65 and TNF-alpha release in PAMs and mice. In contrast, TLR4 knockdown or the use of BAY 11-7082, a specific inhibitor of NF kappa B, blocked the AFB1-promoted SIV replication and inflammatory responses in PAMs. Furthermore, a TLR4-specific antagonist, TAK242, and TLR4 knockout both attenuated the AFB(1)-promoted SIV replication, inflammation and lung damage in mice. We therefore conclude that AFB(1) exposure aggravates SIV replication, inflammation and lung damage by activating TLR4-NF kappa B signaling.
- 出版日期2018-10-4
- 单位南京农业大学
