Uncovering the Dynamics of Immune Cell Populations in the First Week of Life: The Interplay of Neutrophils and Breastfeeding [methylation]

The first few days of life are characterized by rapid external and internal changes that require rapid host adaptations. Despite growing evidence of the impact of this period on an individual’s lifelong health trajectory, this period remains largely uncharted. To decipher key factors associated with changes in peripheral blood cell composition we conducted a stringently standardized, high-throughput immune phenotyping investigation on 796 newborns across diverse settings (The Gambia, West Africa and Papua New Guinea, Australasia) in the framework of a Human Immunology Project Consortium study. Samples were collected twice from each newborn during the first week of life and analyzed via high throughput flow cytometry with an unbiased automated gating algorithm to capture cell compositional changes at an unprecedented level of detail. We found that immune cell composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes with age/day of life were most pronounced in the innate myeloid compartment. While there was minimal impact of sex, season of birth, mother’s age or origin (i.e., environmental and genetic background), breastfeeding and vaccination were strongly associated with increase in cell counts of peripheral blood neutrophils and monocytes. Our results may suggest a possible association of initiation of breastfeeding with changes in immune ontogeny, and thus possibly host immune-mediated protection from infection. These data begin to outline a specific window of opportunity for interventions that can deliberately direct immune ontogeny. longitudinal neonatal cohort study

生命最初数日以快速的外在与内在变化为特征，这要求宿主迅速做出适应性调整。尽管已有越来越多证据表明这一时期对个体终身健康轨迹存在影响，但该阶段仍在很大程度上未被充分探索。为解析与外周血细胞组成变化相关的关键因素，我们在人类免疫学项目联盟（Human Immunology Project Consortium）研究框架下，对来自不同研究场景（西非冈比亚、澳大拉西亚巴布亚新几内亚）的796名新生儿开展了严格标准化的高通量免疫表型分析（high-throughput immune phenotyping）。我们于每名新生儿出生后第一周内采集两次样本，并通过高通量流式细胞术（high throughput flow cytometry）结合无偏自动门控算法（unbiased automated gating algorithm）开展分析，以空前精细的分辨率捕捉细胞组成变化。研究发现，外周血免疫细胞组成的变化模式在不同人群与环境中高度保守。随生命日龄变化的细胞组成差异在先天髓系细胞组分中最为显著。尽管性别、出生季节、母亲年龄或出身（即环境与遗传背景）对细胞组成的影响极小，但母乳喂养与疫苗接种与外周血中性粒细胞和单核细胞的计数升高显著相关。本研究结果提示，母乳喂养启动时机可能与免疫发育（immune ontogeny）存在关联，进而可能帮助宿主获得免疫介导的感染防护能力。本数据集首次为可精准调控免疫发育的干预措施划定了特定的时间窗口。本研究为纵向新生儿队列研究。