TY - JOUR
T1 - Intra-amniotic ureaplasma parvum-induced maternal and fetal inflammation and immune responses in rhesus macaques
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.
PY - 2016/11/15
Y1 - 2016/11/15
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.
KW - chorioamnionitis
KW - decidua
KW - fetal immunology
KW - intrauterine infection
KW - regulatory T-cells
UR - http://www.scopus.com/inward/record.url?scp=85006371844&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006371844&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiw408
DO - 10.1093/infdis/jiw408
M3 - Article
C2 - 27601620
AN - SCOPUS:85006371844
VL - 214
SP - 1597
EP - 1604
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 10
ER -