Group B Streptococcus infection induces M1-like activation in human placental and mouse decidual macrophages.

Abstract

Abstract Group B Streptococcus (GBS), a vaginal colonizing gram-positive bacterium, is a leading cause of neonatal death and sepsis. How GBS evades macrophage defenses in the gravid uterus is not yet known. In response to stimuli, macrophages are activated along a spectrum known as polarization ranging from classically-activated, pro-inflammatory “M1” to alternatively-activated anti-inflammatory “M2” macrophages. These activation states can contribute to disease pathogenesis. This study aims to define changes in macrophage activation in response to GBS infection. Human monocyte derived macrophages (MDMs) were infected with GBS or polarized in vitro with M1 (IFNγ/LPS) or M2 (IL-4 or IL-10) stimuli. Placental macrophages (PMs) were infected with GBS or treated with IFNγ/LPS. To mimic human ascending vaginal infection in vivo, C57BL/6 mice were inoculated vaginally with GBS at day E13.5 for 48h. Subsequently, decidual macrophages were isolated and analyzed for polarization markers via flow cytometry and tissues were used for histology. Resulting phenotypes were characterized using qRT-PCR, ELISA, and flow cytometry. In MDMs, GBS upregulated M1 genes (CCR7, CD80) and downregulated M2 genes (CD209, CD163). GBS increased the release of M1 cytokines (TNFα, IL-1β) in MDMs and PMs. PM surface expression of M1 markers (CCR7, CD80) increased while M2 markers (CD206, CD163, CD209) decreased. Mouse decidual macrophage surface expression of CD206 was downregulated while CD11c exhibited little change. Our results suggest that GBS may induce M1 activation in both human and mouse models. These studies provide new insights into the role of macrophage activation in GBS pathogenesis. Studies supported by NIH NIAID Training Grant 5T32AI007281-27.