Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy

Abstract

Group B Streptococcus (GBS) is a pathobiont that can ascend to the placenta and cause adverse pregnancy outcomes, in part through production of the toxin β‐hemolysin/cytolysin (β‐h/c). Innate immune cells have been implicated in the response to GBS infection, but the impact of β‐h/c on their response is poorly defined. We show that GBS modulates innate immune cell states by subversion of host inflammation through β‐h/c, allowing worse outcomes. We used an ascending mouse model of GBS infection to measure placental cell state changes over time following infection with a β‐h/c‐deficient and isogenic wild type GBS strain. Transcriptomic analysis suggests that β‐h/c‐producing GBS elicit a worse phenotype through suppression of host inflammatory signaling in placental macrophages and neutrophils, and comparison of human placental macrophages infected with the same strains recapitulates these results. Our findings have implications for identification of new targets in GBS disease to support host defense against pathogenic challenge.

Gestational diabetes augments group B Streptococcus infection by disrupting maternal immunity and the vaginal microbiota

“…Neutrophils and macrophages are recruited to gestational tissues and engage various antibacterial strategies to limit ascending GBS infection; 80 , 91 , 92 however, GBS may evade immune responses by dampening activation 93 or evasively hiding in macrophages 94 . Macrophage depletion decreases fetoplacental GBS burdens, but not maternal reproductive burdens, in a mouse model of ascending infection 94 .…”

Gestational diabetes augments group BStreptococcus perinatal infection through disruptions in maternal immunity and the vaginal microbiota

“…Neutrophils and macrophages are recruited to gestational tissues and engage various antibacterial strategies to limit ascending GBS infection 102,115,116 ; however, GBS may evade immune responses by dampening activation 117 or evasively hiding in macrophages 118 . Macrophage depletion decreases fetoplacental GBS burdens, but not maternal reproductive burdens, in a mouse model of ascending infection 118 .…”

Antimicrobial stewardship and targeted therapies in the changing landscape of maternal sepsis

“…This causes local immune defenses to be more permeable to invading organisms, and can also lead to infections overwhelming host responses. [ 104 , 105 ]…”