Intra-amniotic Ureaplasma parvum-Induced Maternal and Fetal Inflammation and Immune Responses in Rhesus Macaques.
Although Ureaplasma species are the most common organisms associated with prematurity, their effects on the maternal and fetal immune system remain poorly characterized.



Rhesus macaque dams at approximately 80% gestation were injected intra-amniotically with 107colony-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.



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.



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.
Perinatal Institute.
Paranthaman
P
Senthamaraikannan
Perinatal Institute.
Pietro
P
Presicce
Perinatal Institute.|Division of Immunobiology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Ohio.
Cesar M
CM
Rueda
Perinatal Institute.|Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Gunlawadee
G
Maneenil
Perinatal Institute.
Augusto F
AF
Schmidt
California National Primate Research Center.|Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis.
Lisa A
LA
Miller
Department of Pathology, University of Alabama at Birmingham.
Ken B
KB
Waites
Perinatal Institute.
Alan H
AH
Jobe
Perinatal Institute.
Suhas G
SG
Kallapur
Perinatal Institute.|Division of Immunobiology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Ohio.
Claire A
CA
Chougnet
D000653:Amniotic Fluid / Q000382:microbiology*; D000818:Animals; D002821:Chorioamnionitis / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004716:Endometritis / Q000276:immunology / Q000473:pathology*; D005260:Female; D005315:Fetal Diseases / Q000276:immunology / Q000473:pathology*; D008253:Macaca mulatta; D011247:Pregnancy; D014509:Ureaplasma / Q000276:immunology* / Q000302:isolation & purification; D016869:Ureaplasma Infections / Q000276:immunology / Q000473:pathology*
chorioamnionitis; decidua; fetal immunology; intrauterine infection; regulatory T-cells