Rosati E, Fettucciari K, Scaringi L, Cornacchione P, Sabatini R, Mezzasoma L, Rossi R, Marconi P
Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, Italy.
Scand J Immunol. 1998 Apr;47(4):314-23. doi: 10.1046/j.1365-3083.1998.00305.x.
This study was undertaken to better understand the complex relationship between specific and non-specific host defence mechanisms and group B streptococci (GBS). A comprehensive kinetics analysis of cytokine mRNA expression was performed, by Northern blot assay, in peritoneal exudate cells (PEC) and spleen cells (SC) recovered from CD-1 mice at various times during the course of an intraperitoneal infection with a lethal dose (5 x 10(3) microorganisms/mouse) of type Ia GBS, reference strain 090 (GBS-Ia). Analysis of cytokines involved in the development of a specific TH response shows that GBS-Ia in PEC induce only a weak increase of IL-2 mRNA expression and in SC a cytokine pattern characterized by IL-2, IFN-gamma and IL-12 in the absence of IL-4, IL-5 and IL-10. This selected cytokine pattern could provide appropriate conditions for the development of a TH1 response. Analysis of inflammatory cytokines, which are usually induced early during an in vivo infection, shows that there is a significant expression of mRNA specific for IL-1beta, TNFalpha and IL-6, both in PEC and SC only at 24 h which persists at a high level until 36 h. This delayed cytokine induction, accompanied by the contemporary activation of splenic phagocytic cells, occurs only when the number of GBS-Ia is extremely high. In fact, at 24 h GBS-Ia have heavily colonized all organs. In vitro infection of thioglycollate-elicited peritoneal macrophages confirms that the ability of GBS-Ia to induce a strong inflammatory cytokine response depends strictly on the number of infecting microorganisms. Indeed, macrophages respond to GBS-Ia with a very rapid induction of IL-1beta and TNFalpha mRNA when infected at a ratio of 1:10, but not at 100:1. Two major observations emerged from this study: (1) GBS-Ia, by inducing a cytokine pattern which seems to favour development of a TH1 response, could evade antibody production essential for resistance to GBS; and (2) inflammatory cytokine response is induced when a heavy microbial invasion of the host has already occurred. These novel features of GBS-Ia could contribute to the development and progression of lethal infection in mice.
本研究旨在更好地理解特异性和非特异性宿主防御机制与B族链球菌（GBS）之间的复杂关系。通过Northern印迹分析，对从CD-1小鼠腹腔内感染致死剂量（5×10³个微生物/小鼠）Ia型GBS参考菌株090（GBS-Ia）过程中不同时间点回收的腹腔渗出细胞（PEC）和脾细胞（SC）中的细胞因子mRNA表达进行了全面的动力学分析。对参与特异性TH应答发展的细胞因子分析表明，PEC中的GBS-Ia仅诱导IL-2 mRNA表达微弱增加，而在SC中，细胞因子模式以IL-2、IFN-γ和IL-12为特征，不存在IL-4、IL-5和IL-10。这种选定的细胞因子模式可为TH1应答的发展提供合适条件。对通常在体内感染早期诱导的炎性细胞因子分析表明，仅在24小时时，PEC和SC中均有IL-1β、TNFα和IL-6特异性mRNA的显著表达，且该表达在高水平持续至36小时。这种延迟的细胞因子诱导，伴随着脾吞噬细胞的同时激活，仅在GBS-Ia数量极高时发生。事实上，在24小时时GBS-Ia已大量定殖于所有器官。巯基乙酸盐诱导的腹腔巨噬细胞的体外感染证实，GBS-Ia诱导强烈炎性细胞因子应答的能力严格取决于感染微生物的数量。确实，当以1:（10）的比例感染时，巨噬细胞对GBS-Ia的应答是IL-1β和TNFα mRNA的非常快速的诱导，但在100:1时则不然。本研究得出两个主要观察结果：（1）GBS-Ia通过诱导一种似乎有利于TH1应答发展的细胞因子模式，可能逃避对GBS抗性至关重要的抗体产生；（2）当宿主发生严重微生物入侵时会诱导炎性细胞因子应答。GBS-Ia的这些新特征可能有助于小鼠致死性感染的发生和进展。
