Departments of Pediatrics and Medicine, University of California, San Francisco, San Francisco, CA, USA.
Immunol Rev. 2020 Jan;293(1):216-229. doi: 10.1111/imr.12806. Epub 2019 Sep 25.
Malaria causes tremendous early childhood morbidity and mortality, providing an urgent impetus for the development of a vaccine that is effective in neonates. However, the infant immune response to malaria may be influenced by events that occur well before birth. Placental malaria infection complicates one quarter of all pregnancies in Africa and frequently results in exposure of the fetus to malaria antigens in utero, while the immune system is still developing. Some data suggest that in utero exposure to malaria may induce immunologic tolerance that interferes with the development of protective immunity during childhood. More recently, however, a growing body of evidence suggests that fetal malaria exposure can prime highly functional malaria-specific T- and B-cells, which may contribute to postnatal protection from malaria. In utero exposure to malaria also impacts the activation and maturation of fetal antigen presenting cells and innate lymphocytes, which could have implications for global immunity in the infant. Here, we review recent advances in our understanding of how various components of the fetal immune system are altered by in utero exposure to malaria, discuss factors that may tilt the critical balance between tolerance and adaptive immunity, and consider the implications of these findings for malaria prevention strategies.
疟疾导致了大量的儿童早期发病和死亡，这为开发一种在新生儿中有效的疫苗提供了紧迫的动力。然而，婴儿对疟疾的免疫反应可能受到出生前发生的事件的影响。胎盘疟疾感染使非洲四分之一的妊娠复杂化，并且经常导致胎儿在子宫内暴露于疟疾抗原，而此时免疫系统仍在发育中。一些数据表明，子宫内暴露于疟疾可能会诱导免疫耐受，从而干扰儿童期保护性免疫的发展。然而，最近越来越多的证据表明，胎儿疟疾暴露可以引发高度功能性的疟疾特异性 T 细胞和 B 细胞，这可能有助于产后免受疟疾的侵害。子宫内暴露于疟疾还会影响胎儿抗原呈递细胞和先天淋巴细胞的激活和成熟，这可能对婴儿的全球免疫产生影响。在这里，我们回顾了最近在理解胎儿免疫系统的各个组成部分如何受到子宫内暴露于疟疾的影响方面的进展，讨论了可能使耐受和适应性免疫之间的关键平衡倾斜的因素，并考虑了这些发现对疟疾预防策略的意义。
