Warren Joanna, Mastroeni Pietro, Dougan Gordon, Noursadeghi Mahdad, Cohen Jonathan, Walport Mark J, Botto Marina
Rheumatology Section, Division of Medicine, Department of Biochemistry, Imperial College School of Medicine London, University of Cambridge, Cambridge, United Kingdom.
Infect Immun. 2002 Feb;70(2):551-7. doi: 10.1128/IAI.70.2.551-557.2002.
The role of the complement system in host defense against Salmonella infection is poorly defined. Bacterial cell wall O-antigen polysaccharide can activate the alternative pathway in vitro. No studies, however, have elucidated the role of the classical pathway in immunity to Salmonella spp. in vivo. C1q-deficient mice (C1qa(-/-)) on a 129/Sv genetic background and strain-matched controls were infected intraperitoneally and intravenously with Salmonella enterica serovar Typhimurium and monitored over a 14-day period. After inoculation by either route, the C1qa(-/-) mice were found to be significantly more susceptible to Salmonella infection. Hepatic and splenic bacterial counts, performed at various time points, showed increased numbers of colonies in complement-deficient mice compared to controls. Analysis of blood clearance showed no difference between the two experimental groups during the first 15 min. However, after 20 min and until 6 h postinfection, numbers of circulating bacteria were significantly higher in complement-deficient mice. In vitro experiments using either resident or thioglycolate-elicited peritoneal macrophages showed a significant increase in the number of bacteria inside C1q-deficient macrophages compared to controls irrespective of the serum used for opsonizing the bacteria. These findings could not be explained either by an increased bacterial uptake, analyzed in vitro and in vivo using green fluorescent protein-tagged salmonellae, or by a defect in the respiratory burst or in NO production. The data presented here suggest the possibility of novel pathways by which C1q may modulate the pathogenesis of infectious diseases caused by intracellular pathogens.
补体系统在宿主抵御沙门氏菌感染中的作用尚不明确。细菌细胞壁O抗原多糖可在体外激活替代途径。然而，尚无研究阐明经典途径在体内对沙门氏菌免疫中的作用。将遗传背景为129/Sv的C1q缺陷小鼠（C1qa(-/-)）及其品系匹配的对照小鼠经腹腔和静脉注射鼠伤寒沙门氏菌，并在14天内进行监测。通过任一途径接种后，发现C1qa(-/-)小鼠对沙门氏菌感染的易感性显著更高。在不同时间点进行的肝脏和脾脏细菌计数显示，与对照相比，补体缺陷小鼠中的菌落数量增加。血液清除分析显示，在最初15分钟内两个实验组之间没有差异。然而，在感染后20分钟直至6小时，补体缺陷小鼠中循环细菌的数量显著更高。使用驻留或巯基乙酸盐诱导的腹腔巨噬细胞进行的体外实验表明，与对照相比，无论用于调理细菌的血清如何，C1q缺陷巨噬细胞内的细菌数量均显著增加。这些发现既不能通过使用绿色荧光蛋白标记的沙门氏菌在体外和体内分析的细菌摄取增加来解释，也不能通过呼吸爆发或一氧化氮产生缺陷来解释。此处呈现的数据表明，C1q可能通过新的途径调节由细胞内病原体引起的传染病的发病机制。
