Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum

Maternal parasitoses modulate fetal immune development, manifesting as altered cellular immunological activity in cord blood that may be linked to enhanced susceptibility to infections in early life. Plasmodium falciparum typifies such infections, with distinct placental infection-related changes in cord blood exemplified by expanded populations of parasite antigen-specific regulatory T cells. Here we addressed whether such early-onset cellular immunological alterations persist through infancy. Specifically, in order to assess the potential impacts of P. falciparum infections either during pregnancy or during infancy, we quantified lymphocyte subsets in cord blood and in infants' peripheral blood during the first year of life. The principal age-related changes observed, independent of infection status, concerned decreases in the frequencies of CD4+, NKdim and NKT cells, whilst CD8+, Treg and Teff cells' frequencies increased from birth to 12 months of age. P. falciparum infections present at delivery, but not those earlier in gestation, were associated with increased frequencies of Treg and CD8+ T cells but fewer CD4+ and NKT cells during infancy, thus accentuating the observed age-related patterns. Overall, P. falciparum infections arising during infancy were associated with a reversal of the trends associated with maternal infection i.e. with more CD4+ cells, with fewer Treg and CD8+ cells. We conclude that maternal P. falciparum infection at delivery has significant and, in some cases, year-long effects on the composition of infants' peripheral blood lymphocyte populations. Those effects are superimposed on separate and independent age- as well as infant infection-related alterations that, respectively, either match or run counter to them.

母体寄生虫感染可调控胎儿免疫发育，表现为脐带血中细胞免疫活性发生改变，这可能与婴儿早期感染易感性升高相关。恶性疟原虫（Plasmodium falciparum）便是这类感染的典型代表，胎盘感染相关的脐带血特征性改变以寄生虫抗原特异性调节性T细胞（regulatory T cell, Treg）群体扩增为典型表现。
本研究旨在探究此类早发性细胞免疫改变是否会持续至婴儿期。
具体而言，为评估妊娠或婴儿期恶性疟原虫感染的潜在影响，我们对婴儿出生后第一年的脐带血及外周血淋巴细胞亚群频率进行了定量检测。研究观察到，不受感染状态影响的主要年龄相关性变化包括：CD4+ T细胞（CD4+）、NKdim细胞（NKdim）及自然杀伤T细胞（NKT）的频率降低，而CD8+ T细胞（CD8+）、调节性T细胞及效应T细胞（effector T cell, Teff）的频率从出生至12月龄时呈升高趋势。
分娩时存在的恶性疟原虫感染（而非妊娠早期的感染）与婴儿期调节性T细胞、CD8+ T细胞频率升高，以及CD4+ T细胞、自然杀伤T细胞频率降低相关，进而强化了上述年龄相关性变化模式。
总体而言，婴儿期发生的恶性疟原虫感染则与母体感染相关的变化趋势相反：即CD4+ T细胞频率升高，而调节性T细胞、CD8+ T细胞频率降低。
本研究结论表明，分娩时母体罹患恶性疟原虫感染，会对婴儿外周血淋巴细胞群体的组成产生显著影响，部分影响甚至可持续一年之久。
此类影响叠加于另外两类独立的、分别与年龄及婴儿感染相关的改变之上——这两类改变要么与母体感染的影响趋势一致，要么与之相悖。