Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Article number8422
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2020

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