Modulation of Th17 and Regulatory T cell responses during murine pregnancy contributes to increased maternal susceptibility to Salmonella Typhimurium infection

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DOIResolve DOI: http://doi.org/10.1016/j.placenta.2017.07.025
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TypeArticle
Journal titlePlacenta
ISSN0143-4004
1532-3102
Volume57
Pages227
AbstractObjectives:Salmonella Typhimurium (ST) infection during pregnancy promotes massive placental infection and fetal loss, but also exacerbated systemic infection and maternal death. The inflammatory Th17 response contributes to immunity to ST infection, whereas successful pregnancy correlates to enhanced anti-inflammatory response by regulatory T cells (Tregs). We aimed to determine how Tregs may modulate Th17 immunity against ST infection during pregnancy. Methods: Mice were infected systemically with ST and bacterial burden was enumerated through colony-forming unit assay. Splenic Th17 and Treg cell numbers were determined through flow cytometry. Serum cytokine expression was analyzed using cytometric bead array. Splenic and/or placental mRNA expression of IL-17A, RORγ-t, IL-10 and TNF was determined through qRT-PCR. The effects of in vivo CD25+ cell depletion on infection kinetics and Th17 response were determined. Results: Enhanced bacterial burden during pregnancy was associated with increased serum inflammatory cytokine signature. Splenic and placental Th17 responses were reduced in pregnant infected mice compared to non-pregnant controls. In contrast, splenic Treg numbers were increased in non-infected pregnant mice relative to their non-pregnant counterparts. CD25+ cell depletion reduced bacterial burden while increasing systemic Th17 response in pregnant infected mice. Conclusion: Thus, downregulation of systemic Th17 responses by Tregs during pregnancy may contribute to exacerbation of ST infection.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number23002268
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Record identifier739b9b50-8f7a-4fed-81c2-72394b489227
Record created2017-09-27
Record modified2017-09-27
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