posted on 2020-03-05, 18:33authored byChen Shen, Yujie Gao, Jun Li, Hongyao Du, Ruijing Liang, Yanhong Sun, Jun Xie, Liyun Dong, Yamin Zhang, Jinjin Zhu, Bo Zhang, Guanxin Shen, Xiang Chen, Jintao Zhu, Juan Tao
Branched
polyethylenimine (BPEI) is a cationic polymer and has
been applied as an antigen carrier in vaccines. However, its intrinsic
adjuvanticity and underlying mechanism remain unclear. Here, we systematically
explored the direct stimulation effects of a series of BPEI on bone-marrow-derived
dendritic cells (BMDCs) in vitro. Only high concentrations
of BPEI with molecular weight (MW) equal
to or greater than 25 kDa showed an immune-activating effect, indicating
that both MW and cationic degree contribute
to this effect. In a charge neutralization experiment, the intrinsic
adjuvanticity of BPEI also demonstrated a cationic degree-dependent
pattern. Moreover, we identified reactive oxygen species (ROS) as
the crucial messengers in BPEI-mediated BMDC activation. However,
high MW and cationic charges from the
BPEI exerted a direct toxicity on dendritic cells, which would restrict
its in vivo applications. Therefore, we introduced
fibroblasts as bystander cells and found that BPEI-treated fibroblasts
passed stimulation effects to BMDCs with undetectable cytotoxicity.
During subcutaneous stimulation, which corresponded to the fibroblast-mediated
coculture system, BPEI induced an inflammatory microenvironment and
local immune cell infiltration without obvious cell death. To the
best of our knowledge, this is the first systematic and incisive investigation
of BPEI’s intrinsic adjuvanticity and its functional exploration
in the presence of bystander cells. This finding paves the way to
advance the BPEI-based vaccines and will give insights into the use
of other immunoactive biomaterials with similar properties.