Type II arabinogalactan from Anoectochilus formosanus induced dendritic cell maturation through TLR2 and TLR4
PHYTOMEDICINE
Authors: Lai, Ching-Yi; Yang, Li-Chan; Lin, Wen-Chuan
Abstract
Background: Polysaccharides, considered as immunomodulators with the capacity to activate immunity against microbial pathogens and tumors, have been employed for their dietary and medical benefits. Purpose: This study investigated the immunomodulatory effect of polysaccharide such as type II arabinogalactan from Anoectochilus formosanus (AGAF) on dendritic cell (DC) maturation and the underlying molecular mechanisms. Methods and results: Exposing DCs to AGAF induces cell maturation, which is characterized by the upregulation of CD86, CD83, CD80, CD40, and MHC class land class II expression through flow cytometry analysis and morphological change without cytotoxicity. In addition, AGAF-triggered DC2.A cells were involved in priming T-cell activation in vitro and in vivo. Transfection of toll-like receptor (TLR) 2 proteins and TLR4 siRNA suppressed DC maturation, suggesting that AGAF induced DC maturation through TLR2 and TLR4. Conclusion: These findings indicate that AGAF may be a potentially effective immunomodulator in stimulating DC maturation. (C) 2015 Published by Elsevier GmbH.
Comparison of morphology, phenotypes and function between cultured human IL-4-DC and IFN-DC
MOLECULAR MEDICINE REPORTS
Authors: Jin, Zhiliang; Fan, Jing; Zhang, Yajuan; Yi, Yongxiang; Wang, Lili; Yin, Dandan; Deng, Tao; Ye, Wei
Abstract
Dendritic cells (DCs) as professional antigen presenting cells, are important in the initiation of the primary immune response. The present study compared the morphology, phenotypes and function between monocyte-derived human DCs produced from a conventional culturing system containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 (IL-4-DC) and DCs generated by the stimulation of GM-CSF and interferon (IFN)-alpha (IFN-DC). When compared with IL-4-DC in morphology, IFN-DC contained more organelles, including endoplasmic reticulum and myelin figures, whereas mature (m)IL-4-DC contained more vacuoles in the cells. The spikes of IFN-DC were shorter and thicker. The expression of phenotypes between immature IFN-DC and IL-4-DC were diverse. Following maturation with tumor necrosis factor-alpha, IFN-DC and IL-4-DC upregulated the expression of cluster of differentiation (CD) 11c and CD83. Conversely, immature IFN-DC and IL-4-DC secreted few inflammatory cytokines including interleukin (IL)-18, IL-23, IL-12p70, IL-1 beta and anti-inflammatory IL-10. Following maturation, large amounts of the cytokines were secreted by these two DCs and mIFN-DC secreted more cytokines compared with mIL-4-DC in general. Furthermore, immature IFN-DC and IL-4-DC loaded with cytomegalovirus (CMV)-pp65 protein were unable to induce the priming of T cells, as evaluated by the intracellular staining with IFN-gamma. Notably, mature DCs exhibited the ability to present CMV-pp65 protein and activate T cells. The mIFN-DC activated a greater proportion of autologous CD4(+) T cells (0.91 vs. 0.31%, P<0.001) and CD8(+) T cells (0.90 vs. 0.48%, P<0.001) to secret IFN-gamma compared with mIL-4-DC. The results suggested that the morphology, phenotypes and cytokine secretion of IFN-DC and IL-4-DC were diverse. The mIFN-DC were more effective in priming and cross-priming T cells when compared with IL-4-DC.