Abstract
In this study, we investigated the effect of λ-carrageenan on the maturation and function of dendritic cells (DCs) and its adjuvant effect on DC-based vaccine. We found that λ-carrageenan dose-dependently decreased the endocytosis of DCs, promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. λ-carrageenan treatment also enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation. In TC-1 tumor mouse model, HPV peptides pulsed λ-carrageenan-DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group. The frequencies of CD4+ and CD8+ T cells in spleens of tumor mice and their activation status were significantly increased in HPV-CGN-DC group, but the frequencies of natural regulatory T cells and CD11b+Gr-1+ cells were significantly decreased. Further, HPV-CGN-DC induced strong CD8+ T cell responses, which are negatively correlated with tumor volumes. The results suggested that λ-carrageenan promoted DC maturation through TLR4 signaling pathway and could be used as the adjuvant in DC-based vaccines.
Highlights
Dendritic cells (DCs), as professional antigen presenting cells (APCs), can capture, process and present antigens to naïve T cells to activate antigen-specific immune responses
We found that λ-carrageenan dose-dependently decreased the endocytosis of dendritic cells (DCs), promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. λ-carrageenan treatment enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation
We showed that the food additive, λ-CGN, promoted the maturation and cytokine production of DCs through TLR4 mediated signaling pathway
Summary
Dendritic cells (DCs), as professional antigen presenting cells (APCs), can capture, process and present antigens to naïve T cells to activate antigen-specific immune responses. Clinical trials of DC-based vaccines carried out in tumor patients have been proved its safety and capacity in the induction of antigen-specific immune responses [4]. Several studies reported that CGN has adjuvant effect on the enhancement of immune responses induced by peptide/protein-based vaccines [12, 18]. It is still elusive whether CGN can regulate the maturation and function of DCs, and as adjuvant enhance the antitumor effect of DC-based vaccine. CGN stimulated DCs pulsed with human papillomavirus (HPV) peptides induced strong HPV-specific CD8+ T cell responses and greatly inhibited tumor growth in TC-1 tumor mouse model
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