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 thei...

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Main Authors: Felicia Kuperwaser, Gal Avital, Michelle J Vaz, Kristen N Noble, Allison N Dammann, Tara M Randis, David M Aronoff, Adam J Ratner, Itai Yanai
Format: Article
Language:English
Published: Springer Nature 2023-02-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.202211021
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author Felicia Kuperwaser
Gal Avital
Michelle J Vaz
Kristen N Noble
Allison N Dammann
Tara M Randis
David M Aronoff
Adam J Ratner
Itai Yanai
author_facet Felicia Kuperwaser
Gal Avital
Michelle J Vaz
Kristen N Noble
Allison N Dammann
Tara M Randis
David M Aronoff
Adam J Ratner
Itai Yanai
author_sort Felicia Kuperwaser
collection DOAJ
description 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.
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institution Kabale University
issn 1744-4292
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publishDate 2023-02-01
publisher Springer Nature
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series Molecular Systems Biology
spelling doaj-art-dcccaae194b04d62b8e18e9e0822de922025-08-20T03:43:31ZengSpringer NatureMolecular Systems Biology1744-42922023-02-0119311710.15252/msb.202211021Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancyFelicia Kuperwaser0Gal Avital1Michelle J Vaz2Kristen N Noble3Allison N Dammann4Tara M Randis5David M Aronoff6Adam J Ratner7Itai Yanai8Institute for Computational Medicine, NYU Grossman School of MedicineInstitute for Computational Medicine, NYU Grossman School of MedicineDepartment of Pediatrics, NYU Grossman School of MedicineDivision of Neonatology, Department of Pediatrics, Vanderbilt University Medical CenterRenaissance School of Medicine at Stony Brook UniversityDepartments of Pediatrics and Molecular Medicine, Morsani School of Medicine, University of South FloridaIndiana University School of MedicineDepartment of Pediatrics, NYU Grossman School of MedicineInstitute for Computational Medicine, NYU Grossman School of MedicineAbstract 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.https://doi.org/10.15252/msb.202211021bacterial infectiongroup B Streptococcus (GBS)host–pathogen interactionsinnate immunityplacenta
spellingShingle Felicia Kuperwaser
Gal Avital
Michelle J Vaz
Kristen N Noble
Allison N Dammann
Tara M Randis
David M Aronoff
Adam J Ratner
Itai Yanai
Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy
Molecular Systems Biology
bacterial infection
group B Streptococcus (GBS)
host–pathogen interactions
innate immunity
placenta
title Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy
title_full Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy
title_fullStr Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy
title_full_unstemmed Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy
title_short Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy
title_sort host inflammatory dynamics reveal placental immune modulation by group b streptococcus during pregnancy
topic bacterial infection
group B Streptococcus (GBS)
host–pathogen interactions
innate immunity
placenta
url https://doi.org/10.15252/msb.202211021
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