Recombinant invasive Lactobacillus plantarum expressing fibronectin binding protein A induce specific humoral immune response by stimulating differentiation of dendritic cells
Liu J., Yang G., Gao X., Zhang Z., Liu Y., Liu Q., Chatel J.-M., Jiang Y., Wang C.
Journal:Beneficial Microbes
IF:2.94
DOI:10.3920/BM2018.0157
PMID:
Published:2019-05-28
research field:疫苗学合成生物学免疫学微生物学
Abstract
Recombinant lactic acid bacteria (LAB), especially Lactococcus lactis, have been genetically engineered to express heterogeneous invasion proteins, such as the fibronectin binding protein A (FnBPA) from Staphylococcus aureus, to increase the invasion ability of the host strains, indicating a promising approach for DNA vaccine delivery. The presence of FnBPA has been also shown to be an adjuvant for co-delivered antigens, however, the underlying mechanisms are still not clear. To explore the above underlying mechanisms, in this study, we constructed a novel Lactobacillus plantarum strain with surface displayed FnBPA, which could significantly improve the adhesion and invasion ratios of L. plantarum strain on a porcine intestinal epithelial cell line (IPEC-J2) about two-fold compared with the empty vector. At the same time, the presence of FnBPA significantly stimulated the differentiation of bone marrow-derived dendritic cells (DCs) and increased the secretion of interleukin (IL)-6 and mRNA level of IL-6 gene, which were proved by flow cytometry, enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription PCR (qRT-PCR). With regard to in vivo study, the presence of FnBPA significantly stimulated the differentiation of DCs in the Peyer's patch (PP) and the percentages of IL-4+ and IL-17A+ T helper (Th) cells of splenocytes in flow cytometry assay. In consistent with these results, the levels of IL-4 and IL-17A in serum as measured via ELISA also increased in mice treated with FnBPA+ L. plantarum. Finally, the FnBPA strain increased the production of B220+ B cells in mesenteric lymph node (MLN) and PP and the levels of FnBPA-specific IgG and sIgA antibodies, indicating the its possible application in vaccine field. This study demonstrated that the invasive L.
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