Xu Jueqiong, Mu Yanjuan, Zhang Yue, Dong Wenyang, Zhu Yinchu, Ma Jiale, Song Wenchao, Pan Zihao, Lu Chengping, Yao Huochun
OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Microb Pathog. 2015 Dec;89:128-39. doi: 10.1016/j.micpath.2015.09.011. Epub 2015 Sep 30.
Pentraxin 3 (PTX3), a soluble pattern recognition receptor, plays an important role in innate immunity and has been implicated to be a candidate resistance gene against Streptococcus suis 2 infection. To discover the antibacterial effect of porcine PTX3 against S. suis 2, the 42-kDa PTX3 protein was expressed by Chinese hamster ovary cells (CHO), and an additional eukaryotic expression vector pVAX-ptx3 was constructed. The expressed porcine PTX3 mediated a range of antibacterial activities including increasing phagocytic capacity of primary porcine alveolar macrophages (PAM) against S. suis 2 and inhibiting adhesion of S. suis 2 to human epidermoid cancer cells (Hep-2). In mouse model, pre-intramuscular injecting with pVAX-ptx3 reduced mortality and reduced bacteria loads in blood, spleen, lung and brain compared with that of control group during 2-12 h following intraperitoneal injection (i.p.) with S. suis 2. Meanwhile, the expressions of IL-6 and IL-8 in blood were increased in pVAX-ptx3 group, whereas no obvious changes about IL-10. In piglet model, bacteria load in blood of pVAX-ptx3 group was significantly lower than that of control group after i.p. with S. suis 2, correspondingly, expression of IL-6 and IL-8 were significantly increased in pVAX-ptx3 group. In contrast, white blood cell (WBC) and neutrophil cell (NEU) count of peripheral blood in pVAX-ptx3 group were lower than that of control group. These studies described a novel antibacterial role for porcine PTX3 against S. suis 2 both in vitro and in vivo and suggested that porcine PTX3 may be a potential biological agent against S. suis 2 in pig and be used for the clinical prevention and treatment of streptococcosis caused by S. suis 2.
五聚体蛋白3(PTX3)是一种可溶性模式识别受体,在固有免疫中发挥重要作用,并且被认为是抗猪链球菌2型感染的候选抗性基因。为了探究猪PTX3对猪链球菌2型的抗菌作用,通过中国仓鼠卵巢细胞(CHO)表达了42 kDa的PTX3蛋白,并构建了一个额外的真核表达载体pVAX-ptx3。所表达的猪PTX3介导了一系列抗菌活性,包括提高原代猪肺泡巨噬细胞(PAM)对猪链球菌2型的吞噬能力以及抑制猪链球菌2型对人表皮样癌细胞(Hep-2)的黏附。在小鼠模型中,与对照组相比,在腹腔注射(i.p.)猪链球菌2型后的2 - 12小时内,预先肌肉注射pVAX-ptx3可降低死亡率并减少血液、脾脏、肺和脑中的细菌载量。同时,pVAX-ptx3组血液中IL-6和IL-8的表达增加,而IL-10没有明显变化。在仔猪模型中,腹腔注射猪链球菌2型后,pVAX-ptx3组血液中的细菌载量显著低于对照组,相应地,pVAX-ptx3组中IL-6和IL-8的表达显著增加。相反,pVAX-ptx3组外周血中的白细胞(WBC)和中性粒细胞(NEU)计数低于对照组。这些研究描述了猪PTX3在体外和体内对猪链球菌2型的一种新的抗菌作用,并表明猪PTX3可能是猪抗猪链球菌2型的一种潜在生物制剂,可用于临床预防和治疗由猪链球菌2型引起的链球菌病。