Soluble RANKL expression in Lactococcus lactis and investigation of its potential as an oral vaccine adjuvant
| Autor: | Ho-Bin Lee, Jin-Duck Bok, Jeong-In Kim, Hui-Shan Li, Chong-Su Cho, Zhong-Shan Hong, Inseon Kim, Yun-Jaie Choi, Da-Chuan Piao, Tae-Eun Park, Sushila Maharjan, Jun-Yeong Lee, Sang-Kee Kang |
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| Jazyk: | angličtina |
| Předmět: |
medicine.medical_treatment
Immunology Administration Oral Gene Expression Biology Mucosal immunization Mice Peyer's Patches Immune system Intestinal mucosa Antigen Adjuvants Immunologic medicine Animals M cells Intestinal Mucosa Receptor Microfold cell Oral adjuvant RANKL L. lactis Vaccines Lactococcus lactis RANK Ligand biology.organism_classification Recombinant Proteins biology.protein Adjuvant Research Article |
| Zdroj: | BMC IMMUNOLOGY(16) BMC Immunology |
| ISSN: | 1471-2172 |
| DOI: | 10.1186/s12865-015-0132-x |
| Popis: | Background To initiate mucosal immune responses, antigens in the intestinal lumen must be transported into gut-associated lymphoid tissue through M cells. Recently, it has been increasingly recognized that receptor activator of NF-kB ligand (RANKL) controls M cell differentiation by interacting with RANK expressed on the sub-epithelium of Peyer’s patches. In this study, we increased the number of M cells using soluble RANKL (sRANKL) as a potent mucosal adjuvant. Results For efficient oral delivery of sRANKL, we constructed recombinant Lactococcus lactis (L. lactis) IL1403 secreting sRANKL (sRANKL-LAB). The biological activity of recombinant sRANKL was confirmed by observing RANK-RANKL signaling in vitro. M cell development in response to oral administration of recombinant L. lactis was determined by 1.51-fold higher immunohistochemical expression of M cell marker GP-2, compared to that of non-treatment group. In addition, an adjuvant effect of sRANKL was examined by immunization of mice with M-BmpB as a model antigen after treatment with sRANKL-LAB. Compared with the wild-type L. lactis group, the sRANKL-LAB group showed significantly increased systemic and mucosal immune responses specific to M-BmpB. Conclusions Our results show that the M cell development by sRANKL-LAB can increase the antigen transcytotic capability of follicle-associated epithelium, and thereby enhance the mucosal immune response, which implies that oral administration of sRANKL is a promising adjuvant strategy for efficient oral vaccination. Electronic supplementary material The online version of this article (doi:10.1186/s12865-015-0132-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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