Harrington Whitney E, Kanaan Sami B, Muehlenbachs Atis, Morrison Robert, Stevenson Philip, Fried Michal, Duffy Patrick E, Nelson J Lee
Department of Pediatrics, University of Washington School of Medicine/Seattle Children's Hospital, Washington.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
J Infect Dis. 2017 May 1;215(9):1445-1451. doi: 10.1093/infdis/jix129.
A mother's infection with placental malaria (PM) can affect her child's susceptibility to malaria, although the mechanism remains unclear. The fetus acquires a small amount of maternal cells and DNA known as maternal microchimerism (MMc), and we hypothesized that PM increases MMc and that MMc alters risk of Plasmodium falciparum malaria during infancy.
In a nested cohort from Muheza, Tanzania, we evaluated the presence and level of cord blood MMc in offspring of women with and without PM. A maternal-specific polymorphism was identified for each maternal-infant pair, and MMc was assayed by quantitative polymerase chain reaction. The ability of MMc to predict malaria outcomes during early childhood was evaluated in longitudinal models.
Inflammatory PM increased the detection rate of MMc among offspring of primigravidae and secundigravidae, and both noninflammatory and inflammatory PM increased the level of MMc. Detectable MMc predicted increased risk of positive blood smear but, interestingly, decreased risk of symptomatic malaria and malaria hospitalization.
The acquisition of MMc may result in increased malaria infection but protection from malaria disease. Future studies should be directed at the cellular component of MMc, with attention to its ability to directly or indirectly coordinate anti-malarial immune responses in the offspring.
母亲感染胎盘疟疾（PM）会影响其孩子对疟疾的易感性，尽管其机制尚不清楚。胎儿会获得少量称为母体微嵌合体（MMc）的母体细胞和DNA，我们推测PM会增加MMc，并且MMc会改变婴儿期感染恶性疟原虫疟疾的风险。
在坦桑尼亚穆赫扎的一个嵌套队列中，我们评估了患有和未患有PM的女性后代脐带血MMc的存在情况和水平。为每对母婴确定了一个母体特异性多态性，并通过定量聚合酶链反应检测MMc。在纵向模型中评估了MMc预测幼儿期疟疾结局的能力。
炎症性PM增加了初产妇和经产妇后代中MMc的检出率，非炎症性和炎症性PM均增加了MMc的水平。可检测到的MMc预测血涂片阳性风险增加，但有趣的是，有症状疟疾和疟疾住院风险降低。
获得MMc可能会增加疟疾感染，但能预防疟疾疾病。未来的研究应针对MMc的细胞成分，关注其直接或间接协调后代抗疟疾免疫反应的能力。
