Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy
Abstract Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CC...
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| Format: | Article |
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Nature Portfolio
2020-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-65422-1 |
| _version_ | 1829465193803939840 |
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| author | Yi-Ju Chou Ching-Cheng Lin Ivan Dzhagalov Nien-Jung Chen Chao-Hsiung Lin Chun-Cheng Lin Szu-Ting Chen Kuo-Hsin Chen Shu-Ling Fu |
| author_facet | Yi-Ju Chou Ching-Cheng Lin Ivan Dzhagalov Nien-Jung Chen Chao-Hsiung Lin Chun-Cheng Lin Szu-Ting Chen Kuo-Hsin Chen Shu-Ling Fu |
| author_sort | Yi-Ju Chou |
| collection | DOAJ |
| description | Abstract Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CCL-34) could induce autophagy to promote innate and adaptive immunity. In addition, the potential of CCL-34 as an immune adjuvant in vivo was also investigated. Our data using RAW264.7 cells and bone marrow-derived macrophages showed that CCL-34 induced autophagy through a TLR4-NF-κB pathway. The autophagy-related molecules (Nrf2, p62 and Beclin 1) were activated in RAW264.7 cells and bone marrow-derived macrophages under CCL-34 treatment. CCL-34-stimulated macrophages exhibited significant antigen-processing activity and induced the proliferation of antigen-specific CD4+T cells as well as the production of activated T cell-related cytokines, IL-2 and IFN-γ. Furthermore, CCL-34 immunization in mice induced infiltration of monocytes in the peritoneal cavity and elevation of antigen-specific IgG in the serum. CCL-34 treatment in vivo did not cause toxicity based on serum biochemical profiles. Notably, the antigen-specific responses induced by CCL-34 were attenuated by the autophagy inhibitor, 3-methyladenine. In summary, we demonstrated CCL-34 can induce autophagy to promote antigen-specific immune responses and act as an efficient adjuvant. |
| first_indexed | 2024-12-13T16:49:27Z |
| format | Article |
| id | doaj.art-1b2b59d6d750445faa8b12ddd17b55b0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:49:27Z |
| publishDate | 2020-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1b2b59d6d750445faa8b12ddd17b55b02022-12-21T23:38:04ZengNature PortfolioScientific Reports2045-23222020-05-0110111510.1038/s41598-020-65422-1Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagyYi-Ju Chou0Ching-Cheng Lin1Ivan Dzhagalov2Nien-Jung Chen3Chao-Hsiung Lin4Chun-Cheng Lin5Szu-Ting Chen6Kuo-Hsin Chen7Shu-Ling Fu8Program in Molecular Medicine, School of Life Sciences, National Yang-Ming University and Academia SinicaInstitute of Microbiology and Immunology, National Yang-Ming UniversityInstitute of Microbiology and Immunology, National Yang-Ming UniversityInstitute of Microbiology and Immunology, National Yang-Ming UniversityDepartment of Life Sciences and Institute of Genome Sciences, National Yang-Ming UniversityDepartment of Chemistry, National Tsing Hua UniversityInstitute of Clinical Medicine, National Yang-Ming UniversityDepartment of Surgery, Far-Eastern Memorial HospitalProgram in Molecular Medicine, School of Life Sciences, National Yang-Ming University and Academia SinicaAbstract Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CCL-34) could induce autophagy to promote innate and adaptive immunity. In addition, the potential of CCL-34 as an immune adjuvant in vivo was also investigated. Our data using RAW264.7 cells and bone marrow-derived macrophages showed that CCL-34 induced autophagy through a TLR4-NF-κB pathway. The autophagy-related molecules (Nrf2, p62 and Beclin 1) were activated in RAW264.7 cells and bone marrow-derived macrophages under CCL-34 treatment. CCL-34-stimulated macrophages exhibited significant antigen-processing activity and induced the proliferation of antigen-specific CD4+T cells as well as the production of activated T cell-related cytokines, IL-2 and IFN-γ. Furthermore, CCL-34 immunization in mice induced infiltration of monocytes in the peritoneal cavity and elevation of antigen-specific IgG in the serum. CCL-34 treatment in vivo did not cause toxicity based on serum biochemical profiles. Notably, the antigen-specific responses induced by CCL-34 were attenuated by the autophagy inhibitor, 3-methyladenine. In summary, we demonstrated CCL-34 can induce autophagy to promote antigen-specific immune responses and act as an efficient adjuvant.https://doi.org/10.1038/s41598-020-65422-1 |
| spellingShingle | Yi-Ju Chou Ching-Cheng Lin Ivan Dzhagalov Nien-Jung Chen Chao-Hsiung Lin Chun-Cheng Lin Szu-Ting Chen Kuo-Hsin Chen Shu-Ling Fu Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy Scientific Reports |
| title | Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy |
| title_full | Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy |
| title_fullStr | Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy |
| title_full_unstemmed | Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy |
| title_short | Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy |
| title_sort | vaccine adjuvant activity of a tlr4 activating synthetic glycolipid by promoting autophagy |
| url | https://doi.org/10.1038/s41598-020-65422-1 |
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