Paranthaman Senthamaraikannan1, Pietro Presicce1, Cesar M Rueda1,2, Gunlawadee Maneenil1,3, Augusto F Schmidt1, Lisa A Miller4,5, Ken B Waites6, Alan H Jobe1, Suhas G Kallapur1, Claire A Chougnet1,2. 1. Perinatal Institute. 2. Division of Immunobiology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Ohio. 3. Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand. 4. California National Primate Research Center. 5. Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis. 6. Department of Pathology, University of Alabama at Birmingham.
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.
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.
Authors: K Motomura; R Romero; V Garcia-Flores; Y Leng; Y Xu; J Galaz; R Slutsky; D Levenson; N Gomez-Lopez Journal: Mol Hum Reprod Date: 2020-09-01 Impact factor: 4.025
Authors: Allison L Fisher; Veena Sangkhae; Pietro Presicce; Claire A Chougnet; Alan H Jobe; Suhas G Kallapur; Sammy Tabbah; Catalin S Buhimschi; Irina A Buhimschi; Tomas Ganz; Elizabeta Nemeth Journal: JCI Insight Date: 2020-02-27
Authors: Christine Silwedel; Matthias C Hütten; Christian P Speer; Christoph Härtel; Axel Haarmann; Birgit Henrich; Maud P M Tijssen; Abdullah Ahmed Alnakhli; Owen B Spiller; Nicolas Schlegel; Silvia Seidenspinner; Boris W Kramer; Kirsten Glaser Journal: Cell Mol Neurobiol Date: 2022-03-25 Impact factor: 5.046
Authors: Kirsten Glaser; Christine Silwedel; Markus Fehrholz; Ana M Waaga-Gasser; Birgit Henrich; Heike Claus; Christian P Speer Journal: Front Cell Infect Microbiol Date: 2017-11-28 Impact factor: 5.293
Authors: Suppawat Boonkasidecha; Paranthaman Senthamarai Kannan; Suhas G Kallapur; Alan H Jobe; Matthew W Kemp Journal: PLoS One Date: 2017-09-28 Impact factor: 3.240