Inflammatory cytokine profile in pregnant women colonized with group B streptococcus reveals IL-17A as a potential biomarker to identify at-risk newborns.

Abstract

Group B Streptococcus (GBS) is a commensal vaginal bacterium that can lead to adverse maternal and neonatal outcomes. In low or middle-income countries, few data are available regarding the immune-inflammatory response in GBS-colonized pregnant mothers and its association with the risk of neonatal invasive disease. In this investigation, we implement a prospective study on a cohort of mother-newborn dyads in Morocco to assess the cytokine profile in GBS-colonized-mothers whose newborns have invasive GBS disease. Pregnant women between 35 and 40 weeks of gestation were screened for vaginal colonization by GBS and followed up until delivery. A panel of inflammatory cytokines was quantified by Luminex multiplex assays and by ELISA in maternal and cord blood, as well as in supernatants after stimulation of pathogen recognition receptors. GBS-colonized-mothers were clustered according to clinical and inflammation markers and to their newborn's infection status. GBS-colonized-mothers whose newborns developed invasive GBS disease exhibited significantly lower IL-1β, IL-4, and IL-17A production compared to GBS-colonized-mothers with healthy newborns. Similar results were obtained following ex vivo stimulation of peripheral blood cells by TLR4 and TLR1/2 ligands. The level of circulating maternal IL-17A had a higher significant predictive value for GBS transmission leading to invasive neonatal disease. This study shows that GBS-colonized-mothers may exhibit a greater cytokine inflammatory response compared to non-colonized-mothers. Regarding mother-newborn dyads, maternal IL-17A, a key mediator of antibacterial defense, emerges as a significant prognostic biomarker for assessing the risk of GBS transmission and the development of neonatal GBS invasive disease.