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

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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

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Ureaplasma
Macaca mulatta
Mothers
Inflammation
Chorioamnionitis
Fetus
Amniotic Fluid
Immune System
Pneumonia
Connexin 43
Connexins
Regulatory T-Lymphocytes
Interferons
Stem Cells
Tumor Necrosis Factor-alpha
Phenotype
Pregnancy
Lung
Brain

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Senthamaraikannan, P., Presicce, P., Rueda, C. M., Maneenil, G., Schmidt, A. F., Miller, L., ... 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

Intra-amniotic ureaplasma parvum-induced maternal and fetal inflammation and immune responses in rhesus macaques. / Senthamaraikannan, Paranthaman; Presicce, Pietro; Rueda, Cesar M.; Maneenil, Gunlawadee; Schmidt, Augusto F.; Miller, Lisa; Waites, Ken B.; Jobe, Alan H.; Kallapur, Suhas G.; Chougnet, Claire A.

In: Journal of Infectious Diseases, Vol. 214, No. 10, 15.11.2016, p. 1597-1604.

Research output: Contribution to journalArticle

Senthamaraikannan, P, Presicce, P, Rueda, CM, Maneenil, G, Schmidt, AF, Miller, L, Waites, KB, Jobe, AH, Kallapur, SG & Chougnet, CA 2016, 'Intra-amniotic ureaplasma parvum-induced maternal and fetal inflammation and immune responses in rhesus macaques', Journal of Infectious Diseases, vol. 214, no. 10, pp. 1597-1604. https://doi.org/10.1093/infdis/jiw408
Senthamaraikannan, Paranthaman ; Presicce, Pietro ; Rueda, Cesar M. ; Maneenil, Gunlawadee ; Schmidt, Augusto F. ; Miller, Lisa ; Waites, Ken B. ; Jobe, Alan H. ; Kallapur, Suhas G. ; Chougnet, Claire A. / Intra-amniotic ureaplasma parvum-induced maternal and fetal inflammation and immune responses in rhesus macaques. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 10. pp. 1597-1604.
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AU - Senthamaraikannan, Paranthaman

AU - Presicce, Pietro

AU - Rueda, Cesar M.

AU - Maneenil, Gunlawadee

AU - Schmidt, Augusto F.

AU - Miller, Lisa

AU - Waites, Ken B.

AU - Jobe, Alan H.

AU - Kallapur, Suhas G.

AU - Chougnet, Claire A.

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N2 - 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.

AB - 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.

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