Chiu C H, Ou J T
Department of Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Microbiol Immunol. 1999;43(1):9-14. doi: 10.1111/j.1348-0421.1999.tb02366.x.
The interaction between Salmonella typhimurium and human polymorphonuclear leukocytes (PMNs) was analyzed in vitro. Three S. typhimurium strains, the wild-type strain OU5043, its isogenic virulence plasmid-cured strain OU5048, and LT2, which represented the types that exhibited three mouse virulence levels, respectively, were used in this study. There was no correlation between the recovery of intracellular S. typhimurium from PMNs and the presence or absence of the virulence plasmid, or the strains' mouse virulence level. When the oxygen-dependent response of PMNs upon phagocytosis of S. typhimurium was examined by checking the intracellular reduction of nitroblue tetrazolium (NBT), the fraction of PMNs that reduced NBT on phagocytosis of the three strains was around 80%, whereas it was 58% with Escherichia coli, 95% with phorbol 12-myristate 13-acetate and 15% with a negative control. Thus there were no significant differences among the three Salmonella strains in terms of their ability to induce the oxidative response in PMNs. Microscopic analysis of Salmonella-infected PMNs indicated that the intracellular Salmonella induced lysis of PMNs. Both OU5043 and OU5048 exhibited a significant intracellular cytotoxic effect on PMNs after 24 hr of infection and this effect was not associated with the presence or absence of the virulence plasmid. On the other hand, lysis of PMNs was related to the intracellular survival of Salmnonella, as ofloxacin, an antibiotic, appeared to be able to protect human PMNs from Salmonella-induced cytotoxicity when this agent was added into the medium to inactivate the intracellular organism. The ability to induce lysis of PMNs by either wild-type or plasmid-cured strains of S. typhimurium may play a crucial role in the pathogenesis of non-typhoid Salmonella. The contribution of pSTV to human salmonellosis is likely to be limited. Furthermore, early institution of antibiotics with a high intracellular activity against Salmonella, such as fluoroquinolones, may be useful to prevent the dissemination of Salmonella infection.
对鼠伤寒沙门氏菌与人多形核白细胞(PMN)之间的相互作用进行了体外分析。本研究使用了三株鼠伤寒沙门氏菌,分别是野生型菌株OU5043、其同基因的无毒力质粒菌株OU5048以及LT2,它们分别代表了表现出三种小鼠毒力水平的类型。从PMN中回收细胞内鼠伤寒沙门氏菌的情况与毒力质粒的有无或菌株的小鼠毒力水平之间没有相关性。当通过检测硝基蓝四唑(NBT)的细胞内还原情况来检查PMN吞噬鼠伤寒沙门氏菌后的氧依赖性反应时,吞噬这三株菌后使NBT还原的PMN比例约为80%,而吞噬大肠杆菌时为58%,吞噬佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯时为95%,阴性对照时为15%。因此,这三株沙门氏菌在诱导PMN氧化反应的能力方面没有显著差异。对感染沙门氏菌的PMN进行显微镜分析表明,细胞内沙门氏菌可诱导PMN裂解。感染24小时后,OU5043和OU5048对PMN均表现出显著的细胞内细胞毒性作用,且这种作用与毒力质粒的有无无关。另一方面,PMN的裂解与沙门氏菌在细胞内的存活有关,因为当将抗生素氧氟沙星添加到培养基中使细胞内细菌失活时,它似乎能够保护人PMN免受沙门氏菌诱导的细胞毒性。鼠伤寒沙门氏菌的野生型或无毒力质粒菌株诱导PMN裂解的能力可能在非伤寒沙门氏菌的发病机制中起关键作用。pSTV对人类沙门氏菌病的贡献可能有限。此外,早期使用对沙门氏菌具有高细胞内活性的抗生素,如氟喹诺酮类,可能有助于预防沙门氏菌感染的传播。