Department of Medicine at the Doherty Institute, University of Melbourne, Melbourne, Australia.
School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
PLoS One. 2020 Jul 29;15(7):e0236375. doi: 10.1371/journal.pone.0236375. eCollection 2020.
Malaria in pregnancy causes maternal, fetal and neonatal morbidity and mortality, and maternal innate immune responses are implicated in pathogenesis of these complications. The effects of malaria exposure and obstetric and demographic factors on the early maternal immune response are poorly understood.
Peripheral blood mononuclear cell responses to Plasmodium falciparum-infected erythrocytes and phytohemagglutinin were compared between pregnant women from Papua New Guinea (malaria-exposed) with and without current malaria infection and from Australia (unexposed). Elicited levels of inflammatory cytokines at 48 h and 24 h (interferon γ, IFN-γ only) and the cellular sources of IFN-γ were analysed.
Among Papua New Guinean women, microscopic malaria at enrolment did not alter peripheral blood mononuclear cell responses. Compared to samples from Australia, cells from Papua New Guinean women secreted more inflammatory cytokines tumor necrosis factor-α, interleukin 1β, interleukin 6 and IFN-γ; p<0.001 for all assays, and more natural killer cells produced IFN-γ in response to infected erythrocytes and phytohemagglutinin. In both populations, cytokine responses were not affected by gravidity, except that in the Papua New Guinean cohort multigravid women had higher IFN-γ secretion at 24 h (p = 0.029) and an increased proportion of IFN-γ+ Vδ2 γδ T cells (p = 0.003). Cytokine levels elicited by a pregnancy malaria-specific CSA binding parasite line, CS2, were broadly similar to those elicited by CD36-binding line P6A1.
Geographic location and, to some extent, gravidity influence maternal innate immunity to malaria.
妊娠疟疾可导致孕产妇、胎儿和新生儿发病率和死亡率，母体固有免疫反应与这些并发症的发病机制有关。疟疾暴露和产科及人口统计学因素对早期母体免疫反应的影响知之甚少。
比较巴布亚新几内亚（疟疾暴露）有和无现症疟疾感染的孕妇与澳大利亚（未暴露）孕妇外周血单个核细胞对恶性疟原虫感染红细胞和植物血凝素的反应。分析 48 小时和 24 小时（仅干扰素-γ）诱导的炎症细胞因子水平和 IFN-γ的细胞来源。
在巴布亚新几内亚妇女中，登记时的镜检疟原虫并未改变外周血单个核细胞的反应。与来自澳大利亚的样本相比，巴布亚新几内亚妇女的细胞分泌更多的炎症细胞因子肿瘤坏死因子-α、白细胞介素 1β、白细胞介素 6 和 IFN-γ；所有检测 p<0.001，并且更多的自然杀伤细胞在响应感染的红细胞和植物血凝素时产生 IFN-γ。在两个群体中，细胞因子反应不受孕次影响，除了在巴布亚新几内亚队列中，多胎妇女在 24 小时时 IFN-γ分泌更高（p=0.029），IFN-γ+Vδ2γδ T 细胞比例更高（p=0.003）。对妊娠疟疾特异性 CSA 结合虫株 CS2 诱导的细胞因子水平与对 CD36 结合虫株 P6A1 诱导的细胞因子水平大致相似。
地理位置以及在一定程度上孕次影响母体对疟疾的固有免疫。
