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Background: Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility. Experimental: We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA257-264) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine. Results: In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen+ cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4+ T, CD8+ T and B cells for immune memory with a strong cellular response. Conclusion: These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response. [ABSTRACT FROM AUTHOR]

Background: The gammadelta T cells serve as early immune defense against certain encountered microbes. Only a few gammadelta T cell-recognized ligands from microbial antigens have been identified so far and the mechanisms by which gammadelta T cells recognize these ligands remain unknown. Here we explored the mechanism of interaction of human gammadelta T cells in peripheral blood with Lipid A (LA)., Results: First, resting gammadelta T cells (mainly Vdelta2 T cells) displayed a strong proliferative response to LA-pulsed monocyte-derived dendritic cells (moDC) and LA-pulsed paraformaldehyde-fixed moDC, but not to free LA in a TCR gammadelta-dependent manner. Second, anti-CD1b or anti-CD1c antibodies could block proliferative response of resting gammadelta T cells to LA-loaded moDC. Besides, only LA-loaded CD1b/CD1c-transfected C1R lymphoblastoma cells (CD1b-/CD1c-C1R) were able to stimulate the proliferation of human gammadelta T cells. Third, the expressions of both Toll-like receptor (TLR)2 and TLR4 on surface of LA-activated gammadelta T cells were upregulated, whereas only anti-TLR4 antibody could partially block their response to LA; Finally LA-loaded moDCs induce gammadelta T cells to produce Th1 cytokines, such as IFN-gamma., Conclusion: Taken together, we found a novel mechanism that human gammadelta T cells recognize LA in a CD1b- or CD1c-restricted manner in first response against Gram-bacteria, while the interaction between TLR4 on gammadelta T cells and LA might strengthen the subsequent response of gammadelta T cells., Reviewers: This article was reviewed by Hao Shen, Youwen He (nominated by Dr. Laurence C Eisenlohr), Dr. Michael Lenardo and Dr. Pushpa Pandiyan.