Institute of Human Virology.
J Infect Dis. 2014 May 15;209(10):1653-62. doi: 10.1093/infdis/jit802. Epub 2013 Dec 10.
Plasmodium falciparum placental infection primes the fetal immune system and alters infant immunity. Mechanisms leading to these outcomes are not completely understood. We focused on Vγ2Vδ2 cells, which are part of the immune response against many pathogens, including P. falciparum. These unconventional lymphocytes respond directly to small, nonpeptidic antigens, independent of major histocompatibility complex presentation. We wondered whether placental malaria, which may increase fetal exposure to P. falciparum metabolites, triggers a response by neonatal Vγ2Vδ2 lymphocytes that can be a marker for the extent of fetal exposure to malarial antigens.
Cord blood mononuclear cells were collected from 15 neonates born to mothers with P. falciparum infection during pregnancy (8 with placental malaria) and 25 unexposed neonates. Vγ2Vδ2 cell phenotype, repertoire, and proliferative responses were compared between newborns exposed and those unexposed to P. falciparum.
Placental malaria-exposed neonates had increased proportions of central memory Vγ2Vδ2 cells in cord blood, with an altered Vγ2 chain repertoire ex vivo and after stimulation.
Our results suggest that placental malaria affects the phenotype and repertoire of neonatal Vγ2Vδ2 lymphocytes. Placental malaria may lower the capacity for subsequent Vγ2Vδ2 cell responses and impair the natural resistance to infectious diseases or the response to pediatric vaccination.
恶性疟原虫胎盘感染使胎儿免疫系统致敏,并改变婴儿的免疫功能。导致这些结果的机制尚不完全清楚。我们专注于 Vγ2Vδ2 细胞,它是针对包括恶性疟原虫在内的许多病原体的免疫反应的一部分。这些非常规淋巴细胞直接对小的非肽类抗原作出反应,而不依赖于主要组织相容性复合体的呈递。我们想知道胎盘疟疾是否会增加胎儿对恶性疟原虫代谢物的暴露,从而引发新生儿 Vγ2Vδ2 淋巴细胞的反应,这种反应可以作为胎儿接触疟原抗原程度的标志物。
从 15 名母亲在妊娠期间感染恶性疟原虫(8 名有胎盘疟疾)的新生儿和 25 名未暴露的新生儿中采集脐血单核细胞。比较暴露和未暴露于恶性疟原虫的新生儿之间 Vγ2Vδ2 细胞表型、 repertoire 和增殖反应。
胎盘疟疾暴露的新生儿脐带血中中央记忆 Vγ2Vδ2 细胞的比例增加,体外和刺激后 Vγ2 链 repertoire 发生改变。
我们的结果表明,胎盘疟疾影响新生儿 Vγ2Vδ2 淋巴细胞的表型和 repertoire。胎盘疟疾可能会降低随后的 Vγ2Vδ2 细胞反应能力,并损害对传染病的天然抵抗力或对儿童疫苗接种的反应。