Kim Tae-Hyoun, Park Jong-Hwan, Park Yeong-Min, Ryu Seung-Wook, Shin Sung Jae, Park Jae-Hak, Kim Dong-Jae
Laboratory Animal Medicine, College of Veterinary Medicine, Seoul University, Seoul 151-742, Republic of Korea; BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Republic of Korea.
Immunobiology. 2015 Jan;220(1):26-31. doi: 10.1016/j.imbio.2014.09.019.
Heat shock protein 70 from Mycobacterium tuberculosis (Mtb Hsp70) has been known to modulate immune response including dendritic cell activation. Muramyl dipeptide (MDP) is an immunoreactive derivative of peptidoglycan from all Gram-negative and Gram-positive bacteria and recognized to be responsible for function of Freund's complete adjuvant. In this study, we evaluated effect of MDP on in vitro activation of bone marrow derived dendritic cells (BMDCs) and in vivo production of cytokines and chemokines induced by Mtb Hsp70. MDP treatment with Mtb Hsp70 dramatically increased production of IL-6, IL-12p40 and TNF-α in BMDCs compared with Mtb Hsp70 alone whereas these effects were abolished in Nod2-deficient BMDCs. Phosphorylation of IκB-α and ERK and impairment of phagocytosis, which is an indicator of DC maturation were enhanced by MDP co-treatment with Mtb hsp70 in BMDCs. In addition, ability of Mtb Hsp70-stimulated BMDCs to induce IFN-γ productions of T cells was increased by MDP co-treatment. Finally, intraperitoneal injection of MDP with Mtb Hsp70 dramatically increased production of IL-6, CXCL-1 and CCL2 in serum compared with Mtb hsp70 injection. Our study showed the synergistic effects of MDP with Mtb Hsp70 on DCs and in vivo immune activation. The use of MDP with Mtb Hsp70 to induce immune activation may provide an effective strategy for vaccination to treat cancer and protect against pathogens.
已知结核分枝杆菌的热休克蛋白70（Mtb Hsp70）可调节免疫反应，包括树突状细胞的激活。胞壁酰二肽（MDP）是所有革兰氏阴性菌和革兰氏阳性菌肽聚糖的免疫反应性衍生物，被认为是弗氏完全佐剂发挥功能的原因。在本研究中，我们评估了MDP对体外骨髓来源树突状细胞（BMDCs）激活的影响，以及对Mtb Hsp70诱导的体内细胞因子和趋化因子产生的影响。与单独使用Mtb Hsp70相比，MDP与Mtb Hsp70共同处理可显著增加BMDCs中IL-6、IL-12p40和TNF-α的产生，而在Nod2缺陷的BMDCs中这些作用消失。MDP与Mtb hsp70共同处理可增强BMDCs中IκB-α和ERK的磷酸化以及吞噬作用的受损，吞噬作用是DC成熟的一个指标。此外，MDP共同处理可增加Mtb Hsp70刺激的BMDCs诱导T细胞产生IFN-γ的能力。最后，与注射Mtb hsp70相比，腹腔注射MDP与Mtb Hsp70可显著增加血清中IL-6、CXCL-1和CCL2的产生。我们的研究显示了MDP与Mtb Hsp70对DCs和体内免疫激活的协同作用。使用MDP与Mtb Hsp70诱导免疫激活可能为治疗癌症和预防病原体感染的疫苗接种提供一种有效策略。
