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).

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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。一项研究使用了32只不同胎次的恒河猴，通过3次连续怀孕感染疟疾(Coatneyi)，从2000年开始，到2006年结束，共有104例慢性感染(113天)。同一只猴子的反复感染代表了不同水平的疟疾免疫。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。剖宫产术中采集婴儿、胎盘、脐带血、母血和羊水。确定了疟疾严重程度增加或减少及其对胎儿/婴儿影响的相关因素。对照组的不良婴儿结局(PIO)特征包括：母亲体重低、胎盘小、LBW、对称性宫内生长迟缓(IUGR)，除绒毛膜羊膜炎外，无相关胎盘病理改变。感染疟疾的孕期PIO包括：高寄生虫、胎盘小、胎儿死亡、LBW、对称性和非对称性IUGR、孕酮和雌二醇不足、产妇体重低以及疟疾相关胎盘病理增加。通过FACS分析(发表于2005年)和对孕妇血清细胞因子的评估，确定了与妊娠和疟疾相关的免疫抑制和免疫病理学。我们检测了初孕、疟疾感染及两者结合过程中外周血中肿瘤坏死因子α及其可溶性受体STNFR1和sTNFR2的水平。肿瘤坏死因子α总是与胎儿死亡有关，而可溶性肿瘤坏死因子受体可能通过中和肿瘤坏死因子α的毒性效应而在胎儿保护中发挥重要作用。我们的研究结果表明，sTNFR2的增加与疟疾有关，而与正常妊娠或因绒毛膜羊膜炎导致的LBW无关。相反，STNFR1在正常妊娠后期的升高表明，在为正常分娩和分娩做准备的过程中，它可能是调节肿瘤坏死因子α的重要因素(在新闻中)。