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| Status |
Public on Apr 26, 2016 |
| Title |
A bacterial hemolytic lipid toxin subverts neutrophils and neutrophil extracellular traps to promote gbs invasion, fetal injury and preterm labor in nonhuman primates |
| Platform organism |
Macaca fascicularis |
| Sample organism |
Macaca nemestrina |
| Experiment type |
Expression profiling by array
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| Summary |
Preterm birth is a leading cause of neonatal morbidity and mortality. Microbial infection and inflammation of the amniotic cavity are associated with the majority of early preterm births and thought to arise from ascension of bacteria from the lower genital tract. Group B Streptococci (GBS) are beta-hemolytic, gram-positive bacteria, which commonly colonize the vagina and have been recovered from the amniotic fluid in cases of preterm birth. Host immune defenses that are critical for prevention of microbial invasion of the amniotic cavity (MIAC) and preterm labor are not completely understood. We recently showed that increased expression of the hemolytic pigment promotes GBS penetration of human placenta ex vivo and hyperhemolytic/hyperpigmented GBS strains with mutations in the hemolysin repressor (CovR/CovS) can be isolated from women in preterm labor. To understand placental/ choriodecidual immune responses that are necessary to prevent MIAC and preterm labor, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. We observed that preterm labor, MIAC, and fetal injury occurred significantly more frequently in pregnant nonhuman primates infected with hyperpigmented GBS (ΔcovR) despite the strong induction of proinflammatory responses in the chorioamnion. Placental histopathology revealed a systematic progression in development of chorioamnionitis in GBSΔcovR animals beginning with chorionic vasculitis and subsequently progressing to neutrophilic infiltration in the chorioamnion.
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| Overall design |
In this study, eleven chronically catheterized pregnant NHP (Macaca nemestrina) containing catheters surgically implanted via laparotomy into the maternal femoral vein, amniotic cavity, and choriodecidual interface in the lower uterine segment (between uterine muscle and fetal membranes, external to amniotic fluid) received one of two experimental treatments: i.e. choriodecidual inoculation of either GBS COH1ΔcovR (n=6; hyperpigmented strain) or GBS COH1ΔcovRΔcylE (n=6; isogenic, nonpigmented strain). Results obtained from these animals were compared to saline controls (n=5; choriodecidual and amniotic fluid saline inoculations) that were performed previously.
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| Contributor(s) |
Boldenow E, Bierle C, Gendrin C, Ngo L, Vornhagen J, Merillat S, Armistead B, Whidbey C, Alishetti V, Ogle J, Gough M, Srinouanprachanh S, MacDonald JW, Bammler TK, Bansal A, Liggitt HD, Rajagopal L, Adams Waldorf KM |
| Citation(s) |
27819066 |
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| Submission date |
Apr 13, 2016 |
| Last update date |
Dec 06, 2016 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
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| Organization name |
University of Washington
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| Department |
Environmental and Occupational Health Sciences
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| Street address |
4225 Roosevelt Way NE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
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| Platforms (1) |
| GPL21725 |
Affymetrix Cynomolgus Gene 1.0 ST |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA318477 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80248_RAW.tar |
69.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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