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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b2b59d6d750445faa8b12ddd17b55b0
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spelling	oai:doaj.org-article:1b2b59d6d750445faa8b12ddd17b55b02021-12-02T14:58:45ZVaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy10.1038/s41598-020-65422-12045-2322https://doaj.org/article/1b2b59d6d750445faa8b12ddd17b55b02020-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-65422-1https://doaj.org/toc/2045-2322Abstract 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.Yi-Ju ChouChing-Cheng LinIvan DzhagalovNien-Jung ChenChao-Hsiung LinChun-Cheng LinSzu-Ting ChenKuo-Hsin ChenShu-Ling FuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	vaccine adjuvant activity of a tlr4-activating synthetic glycolipid by promoting autophagy
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/1b2b59d6d750445faa8b12ddd17b55b0
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Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy

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