A RHESUS MONKEY MODEL OF MALARIA DURING PREGNANCY

怀孕期间疟疾的恒河猴模型

• 批准号: 7348973
• 负责人: BILLIE B DAVISON
• 金额: $ 3.1万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348973
• 关键词: RHESUS; MONKEY; MODEL; MALARIA; DURING

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The associated factors responsible for the increased severity of clinical malaria in pregnant women and its associated fetal complications such as low birth weight (LBW) are unknown. A study utilizing 32 rhesus monkeys of differing parities through 3 sequential pregnancies with malaria (Plasmodium coatneyi) began in 2000 and ended in 2006 with a total of 104 chronic infections (113 days). Repeated infections in the same monkey represented different levels of malaria immunity. Parasitemia, CBCs, FACS data, and clinical signs were monitored and fetal growth and development evaluated by ultrasonography. The infants, placentas, cord blood, maternal blood, and amniotic fluid were collected during cesarean section. Correlates of increased or decreased severity of malaria and its effect on the fetus/infant were identified. Features of poor infant outcome (PIO) in controls included: low weight mother, small placenta, LBW, symmetric intrauterine growth retardation (IUGR), and no associated placental pathology other than chorioamnionitis. PIO in malaria-infected pregnancies included: high parasites, small placenta, fetal death, LBW, symmetric and asymmetric IUGR, insufficient progesterone and estradiol, low maternal weight, and increased malaria-associated placental pathology. Pregnancy-related and malaria-induced immunosuppression and immunopathology were identified though FACS analysis (published 2005) and assessment of maternal serum cytokines. We determined peripheral blood serum levels of TNF alpha, its soluble receptors, STNFR1 and STNFR2, throughout primigravid pregnancy, malaria infection and a combination of the two. TNF alpha was always associated with fetal death and soluble TNF receptors appear to be important for fetal protection possibly through neutralizing the toxic effects of TNF alpha. Our findings showed that increased STNFR2 was associated specifically with malaria and not normal pregnancy or even pregnancy with LBW due to chorioamnionitis. In contrast, elevations in STNFR1 during the later half of normal pregnancy indicate that it may be important in regulating TNF alpha in preparation for normal labor and delivery (in press).

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。导致孕妇临床疟疾严重程度增加的相关因素及其相关的胎儿并发症，如低出生体重（LBW）尚不清楚。一项研究于2000年开始，利用32只不同胎次的恒河猴连续3次怀孕感染疟疾（革内疟原虫），并于2006年结束，共发生104例慢性感染（113天）。同一只猴子的多次感染代表了不同程度的疟疾免疫。监测寄生虫血症、CBCs、FACS数据和临床体征，并通过超声检查评估胎儿生长发育。在剖宫产术中采集婴儿、胎盘、脐带血、母体血和羊水。确定了疟疾严重程度增加或减少的相关因素及其对胎儿/婴儿的影响。对照组婴儿预后差（PIO）的特征包括：母亲体重低、胎盘小、体重过低、对称型宫内生长迟缓（IUGR），除绒毛膜羊膜炎外无相关胎盘病理。疟疾感染妊娠的PIO包括：高寄生虫、小胎盘、胎儿死亡、低体重、对称和不对称IUGR、黄体酮和雌二醇不足、母亲体重低以及疟疾相关胎盘病理增加。通过FACS分析（2005年发表）和母体血清细胞因子评估，确定了妊娠相关和疟疾引起的免疫抑制和免疫病理。我们测定了初孕、疟疾感染和两者结合期间外周血中TNF α及其可溶性受体STNFR1和STNFR2的水平。TNF - α总是与胎儿死亡相关，可溶性TNF受体似乎对胎儿保护很重要，可能是通过中和TNF - α的毒性作用。我们的研究结果表明，STNFR2的增加与疟疾特异性相关，而与正常妊娠无关，甚至与绒毛膜羊膜炎引起的LBW妊娠无关。相反，STNFR1在正常妊娠后半期的升高表明，它可能在调节TNF α为正常产程和分娩做准备时发挥重要作用。