Cytokine response to group B streptococcus infection in mice.

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.