CYTOKINE RESPONSE TO GROUP-B STREPTOCOCCUS INFECTION IN MICE

This study was undertaken to better understand the complex relationshi p between specific and non-specific host defence mechanisms and group B streptococci (GBS). A comprehensive kinetics analysis of cytokine mR NA expression was performed, by Northern blot assay, in peritoneal exu date cells (PEC) and spleen cells (SC) recovered from CD-1 mice at var ious times during the course of an intraperitoneal infection with a le thal dose (5 x 10(3) microorganisms/mouse) of type Ia GBS, reference s train 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 characte rized by IL-2, IFN-gamma and IL-12 in the absence of IL-4, 1L-5 and IL -10. This selected cytokine pattern could provide appropriate conditio ns for the development of a T(H)1 response. Analysis of inflammatory c ytokines, which are usually induced early during an in vivo infection, shows that there is a significant expression of mRNA specific for IL- 1 beta, TNF alpha and IL-6, both in PEC and SC only at 24 h which pers ists at a high level until 36 h. This delayed cytokine induction, acco mpanied by the contemporary activation of splenic phagocytic cells, oc curs 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 thio glycollate-elicited peritoneal macrophages confirms that the ability o f GBS-Ia to induce a strong inflammatory cytokine response depends str ictly on the number of infecting microorganisms. Indeed, macrophages r espond to GBS-Ia with a very rapid induction of IL-1 beta and TNF alph a mRNA when infected at a ratio of 1:10, but not at 100:1. Two major o bservations emerged from this study: (1) GBS-Ia, by inducing a cytokin e pattern which seems to favour development of a T(H)1 response, could evade antibody production essential for resistance to GBS; and (2) in flammatory cytokine response is induced when a heavy microbial invasio n of the host has already occurred. These novel features of GBS-Ia cou ld contribute to the development and progression of lethal infection i n mice.