title: Group BStreptococcusInduces Neutrophil Recruitment to Gestational Tissues and Elaboration of Extracellular Traps and Nutritional Immunity.
abstract: Streptococcus agalactiae, or Group BStreptococcus(GBS), is a gram-positive bacterial pathogen associated with infection during pregnancy and is a major cause of morbidity and mortality in neonates. Infection of the extraplacental membranes surrounding the developing fetus, a condition known as chorioamnionitis, is characterized histopathologically by profound infiltration of polymorphonuclear cells (PMNs, neutrophils) and greatly increases the risk for preterm labor, stillbirth, or neonatal GBS infection. The advent of animal models of chorioamnionitis provides a powerful tool to study host-pathogen relationshipsin vivoandex vivo. The purpose of this study was to evaluate the innate immune response elicited by GBS and evaluate how antimicrobial strategies elaborated by these innate immune cells affect bacteria. Our work using a mouse model of GBS ascending vaginal infection during pregnancy reveals that clinically isolated GBS has the capacity to invade reproductive tissues and elicit host immune responses including infiltration of PMNs within the choriodecidua and placenta during infection, mirroring the human condition. Upon interacting with GBS, murine neutrophils elaborate DNA-containing extracellular traps, which immobilize GBS and are studded with antimicrobial molecules including lactoferrin. Exposure of GBS to holo- or apo-forms of lactoferrin reveals that the iron-sequestration activity of lactoferrin represses GBS growth and viability in a dose-dependent manner. Together, these data indicate that the mouse model of ascending infection is a useful tool to recapitulate human models of GBS infection during pregnancy. Furthermore, this work reveals that neutrophil extracellular traps ensnare GBS and repress bacterial growth via deposition of antimicrobial molecules, which drive nutritional immunity via metal sequestration strategies.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Vishesh
authors.initials: V
authors.lastname: Kothary
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Doster
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rogers
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Kirk
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Joann
authors.initials: J
authors.lastname: Romano-Keeler
authors.affiliation: Department of Medicine, Vanderbilt University Medical CenterNashville, TN, USA; Department of Biomedical Sciences, Grand Valley State UniversityGrand Rapids, MI, USA.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Haley
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University East Lansing, MI, USA.
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Manning
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
authors.affiliation: Department of Medicine, Vanderbilt University Medical CenterNashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare SystemsNashville, TN, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gaddy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D004195:Disease Models, Animal; D065206:Extracellular Traps; D005260:Female; D007113:Immunity, Innate; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology*; D020556:Neutrophil Infiltration; D060737:Reproductive Tract Infections / Q000276:immunology / Q000473:pathology*; D013292:Streptococcus agalactiae / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D000900:Anti-Bacterial Agents; D007501:Iron; D007781:Lactoferrin
keywords: Streptococcus agalactiae; group B Streptococcus; metal; neutrophils; pregnancy