Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor

Erica Boldenow, Claire Gendrin, Lisa Ngo, Craig Bierle, Jay Vornhagen, Michelle Coleman, Sean Merillat, Blair Armistead, Christopher Whidbey, Varchita Alishetti, Veronica Santana-Ufret, Jason Ogle, Michael Gough, Sengkeo Srinouanprachanh, James W. MacDonald, Theo K. Bammler, Aasthaa Bansal, H. Denny Liggitt, Lakshmi Rajagopal, Kristina M. Adams Waldorf

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with most early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B streptococci (GBS) are b-hemolytic, Gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we used a chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC, and immune responses during pregnancy-associated infections. We show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared with nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared with maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor.

Original languageEnglish (US)
Article numbereaah4576
JournalScience Immunology
Volume1
Issue number4
DOIs
StatePublished - 2016
Externally publishedYes

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    Boldenow, E., Gendrin, C., Ngo, L., Bierle, C., Vornhagen, J., Coleman, M., Merillat, S., Armistead, B., Whidbey, C., Alishetti, V., Santana-Ufret, V., Ogle, J., Gough, M., Srinouanprachanh, S., MacDonald, J. W., Bammler, T. K., Bansal, A., Denny Liggitt, H., Rajagopal, L., & Adams Waldorf, K. M. (2016). Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor. Science Immunology, 1(4), [eaah4576]. https://doi.org/10.1126/sciimmunol.aah4576