Zhang Guiqiang, Jia Peiyuan, Liu Hongtao, Hu Tao, Du Yuguang
University of Chinese Academy of Sciences, Beijing 100049, PR China; Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA and State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA and State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
Immunobiology. 2018 Nov;223(11):663-670. doi: 10.1016/j.imbio.2018.07.012. Epub 2018 Jul 6.
Porcine circovirus type 2 (PCV2)-associated diseases have led to great economic losses to the pig industry. Our lab previously found that conjugation of chitosan oligosaccharides (COS) or via a carrier protein enhanced the immunogenicity of PCV2 vaccine against infectious pathogens. However, precise mechanisms and signal transduction pathways underlying the efficacy of COS conjugation remains poorly defined. In this study, to better understand the effects and mechanism of COS conjugates maintain the adjuvant potential in vivo, we investigated its augmentation of macrophage function, including cell activation, NO production, cytokine production and phagocytosis. Additionally, the role of Toll-like receptors (TLR) proteins in this process was also assessed. The results indicate that, as compared to the PCV and PCV/COS, conjugation of COS effectively enhanced the NO production, cytokines generation and phagocytosis activity of macrophages. Noticeably, the generation of NO and proinflammatory cytokines was closely related to the TLR2/4 signaling pathways, strongly suggesting that conjugation of COS regulates innate and adaptive immunity by activation of macrophages, resulting in immune enhancement. In summary, the present study provides a potential mechanism of COS conjugation as a novel adjuvant to improve immune responses against various diseases.
猪圆环病毒2型（PCV2）相关疾病给养猪业造成了巨大的经济损失。我们实验室先前发现，壳寡糖（COS）的偶联或通过载体蛋白可增强PCV2疫苗对感染性病原体的免疫原性。然而，COS偶联物发挥功效的精确机制和信号转导途径仍不清楚。在本研究中，为了更好地理解COS偶联物在体内维持佐剂潜力的效果和机制，我们研究了其对巨噬细胞功能的增强作用，包括细胞活化、一氧化氮（NO）产生、细胞因子产生和吞噬作用。此外，还评估了Toll样受体（TLR）蛋白在此过程中的作用。结果表明，与PCV和PCV/COS相比，COS的偶联有效地增强了巨噬细胞的NO产生、细胞因子生成和吞噬活性。值得注意的是，NO和促炎细胞因子的产生与TLR2/4信号通路密切相关，强烈表明COS的偶联通过激活巨噬细胞来调节先天性和适应性免疫，从而导致免疫增强。总之，本研究提供了COS偶联作为新型佐剂改善针对各种疾病免疫反应的潜在机制。
