Molecular mechanisms underlying protection against H9N2 influenza virus challenge in mice by recombinant Lactobacillus plantarum with surface displayed HA2-LTB

Molecular mechanisms underlying protection against H9N2 influenza virus challenge in mice by recombinant Lactobacillus plantarum with surface displayed HA2-LTB
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表面显示HA2-LTB的重组植物乳杆菌保护小鼠免受H9N2流感病毒攻击的分子机制

DOI:
10.1016/j.jbiotec.2017.08.011
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发表时间:
2017-10-10
影响因子:
4.1
通讯作者:
Wang, Chunfeng
Wang, Chunfeng
中科院分区:
工程技术3区
文献类型:
--
作者:
Jiang, Yanlong;Yang, Guilian;Wang, Chunfeng

文献摘要

被引文献

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禽流感病毒(AIV)对养禽业造成了严重的威胁。本研究构建了一系列重组植物乳杆菌(Lactobacillus plantarum,L.以BalB/c小鼠为模型,研究了重组L. plantarum(L. plantarum)与表面展示血凝素亚基2(HA 2)单独或与产肠毒素大肠杆菌不耐热毒素B亚基(LTB)联合作用的保护作用。结果显示,LTB的存在显著增加了脾和MLN中CD 3(+)CD 4(+)IL-4(+)、CD 3(+)CD 4(+)IFN-γ(+)和CD 3(+)CD 4(+)IL-17(+)T细胞的百分比,以及CD 3(+)CD 8(+)IFN-γ(+)T细胞的百分比。酶联免疫吸附测定(ELISA)也证实了类似的血清IFN-γ的产生增加。洛杉矶具有表面展示HA 2-LTB的植物还显著增加了派伊尔斑中B220(+)伊加(+)B细胞的百分比,这与通过ELISA测定的粘膜SIgA抗体的产生增加一致。最后,口服施用的HA 2-LTB表达菌株有效地保护小鼠免受H9 N2亚型AIV攻击,这在组织病理学分析中通过增加的存活百分比、体重增加和减少的肺部病变显示。总之,本研究提供了LTB对重组乳酸菌产生的异源抗原的佐剂效应的更详细的机制。
It has been considered that the Avian influenza virus (AIV) causes severe threats to poultry industry. In this study, we constructed a series of recombinant Lactobacillus plantarum (L. plantarum) with surface displayed hemagglutinin subunit 2 (HA2) alone or together with heat-labile toxin B subunit (LTB) from enterotoxigenic Escherichia coll. Balb/c mice were used as model to evaluate the protective effects of recombinant L. plantarum strains against H9N2 subtype challenge.The results showed that the presence of LTB significantly increased the percentages of CD3(+)CD4(+)IL-4(+), CD3(+)CD4(+)IFN-gamma(+) and CD3(+)CD4(+)IL-17(+) T cells, as well as CD3(+)CD8(+)IFN-gamma(+) T cells in spleen and MLNs determined by Fluorescence-Activated Cell Sorting assay. Similar increased production of serum IFN-gamma was also confirmed by enzyme linked immunosorbent assay (ELISA). The L. plantarum with surface displayed HA2-LTB also dramatically increased the percentages of B220(+) IgA(+) B cells in peyer patch, in consistent with elevated production of mucosal SIgA antibody determined by ELISA. Finally, the orally administrated HA2-LTB expressing strain efficiently protected mice against H9N2 subtype AIV challenge shown by increased survival percentages, body weight gains and decreased lung lesions in histopathologic analysis. In conclusion, this study provides more detail mechanisms underlying the adjuvant effects of LTB on heterologous antigen produced in recombinant lactic acid bacteria.