Intra-amniotic ureaplasma parvum-induced maternal and fetal inflammation and immune responses in rhesus macaques

Paranthaman Senthamaraikannan, Pietro Presicce, Cesar M. Rueda, Gunlawadee Maneenil, Augusto F. Schmidt, Lisa Miller, Ken B. Waites, Alan H. Jobe, Suhas G. Kallapur, Claire A. Chougnet

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background. Although Ureaplasma species are the most common organisms associated with prematurity, their effects on the maternal and fetal immune system remain poorly characterized. Methods. Rhesus macaque dams at approximately 80% gestation were injected intra-amniotically with 107 colony-forming units of Ureaplasma parvum or saline (control). Fetuses were delivered surgically 3 or 7 days later. We performed comprehensive assessments of inflammation and immune effects in multiple fetal and maternal tissues. Results. Although U. parvum grew well in amniotic fluid, there was minimal chorioamnionitis. U. parvum colonized the fetal lung, but fetal systemic microbial invasion was limited. Fetal lung inflammation was mild, with elevations in CXCL8, tumor necrosis factor (TNF) α, and CCL2 levels in alveolar washes at day 7. Inflammation was not detected in the fetal brain. Significantly, U. parvum decreased regulatory T cells (Tregs) and activated interferon γ production in these Tregs in the fetus. It was detected in uterine tissue by day 7 and induced mild inflammation and increased expression of connexin 43, a gap junction protein involved with labor. Conclusions. U. parvum colonized the amniotic fluid and caused uterine inflammation, but without overt chorioamnionitis. It caused mild fetal lung inflammation but had a more profound effect on the fetal immune system, decreasing Tregs and polarizing them toward a T-helper 1 phenotype.

Original languageEnglish (US)
Pages (from-to)1597-1604
Number of pages8
JournalJournal of Infectious Diseases
Volume214
Issue number10
DOIs
StatePublished - Nov 15 2016

Keywords

  • chorioamnionitis
  • decidua
  • fetal immunology
  • intrauterine infection
  • regulatory T-cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Senthamaraikannan, P., Presicce, P., Rueda, C. M., Maneenil, G., Schmidt, A. F., Miller, L., Waites, K. B., Jobe, A. H., Kallapur, S. G., & Chougnet, C. A. (2016). Intra-amniotic ureaplasma parvum-induced maternal and fetal inflammation and immune responses in rhesus macaques. Journal of Infectious Diseases, 214(10), 1597-1604. https://doi.org/10.1093/infdis/jiw408