title: Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection.
abstract: Ascending infection of microbes from the lower genital tract into the amniotic cavity increases the risk of preterm birth, stillbirth, and newborn infections. Host defenses that are critical for preventing ascending microbial infection are not completely understood. Group BStreptococcus(GBS) are Gram-positive bacteria that frequently colonize the lower genital tract of healthy women but cause severe infections during pregnancy, leading to preterm birth, stillbirth, or early-onset newborn infections. We recently described that the GBS pigment is hemolytic, and increased pigment expression promotes GBS penetration of human placenta. Here, we show that the GBS hemolytic pigment/lipid toxin and hyperpigmented GBS strains induce mast cell degranulation, leading to the release of preformed and proinflammatory mediators. Mast cell-deficient mice exhibit enhanced bacterial burden, decreased neutrophil mobilization, and decreased immune responses during systemic GBS infection. In a vaginal colonization model, hyperpigmented GBS strains showed increased persistence in mast cell-deficient mice compared to mast cell-proficient mice. Consistent with these observations, fewer rectovaginal GBS isolates from women in their third trimester of pregnancy were hyperpigmented/hyperhemolytic. Our work represents the first example of a bacterial hemolytic lipid that induces mast cell degranulation and emphasizes the role of mast cells in limiting genital colonization by hyperpigmented GBS.
authors.affiliation: Department of Pediatric Infectious Diseases, University of Washington, Seattle, WA 98101, USA ; Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Gendrin
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101, USA ; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Vornhagen
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ngo
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101, USA ; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Whidbey
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Boldenow
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Santana-Ufret
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Clauson
authors.affiliation: Department of Pediatric Infectious Diseases, University of Washington, Seattle, WA 98101, USA.
authors.forename: Kellie
authors.initials: K
authors.lastname: Burnside
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Dionne P
authors.initials: DP
authors.lastname: Galloway
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kristina M.
authors.initials: KM
authors.lastname: Adams Waldorf
authors.affiliation: Department of Pediatric Infectious Diseases, University of Washington, Seattle, WA 98101, USA ; Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Piliponsky
authors.affiliation: Department of Pediatric Infectious Diseases, University of Washington, Seattle, WA 98101, USA ; Seattle Children's Research Institute, Seattle, WA 98101, USA ; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajagopal