Immune Dysfunction as a Cause and Consequence of Malnutrition.
Immune Dysfunction as a Cause and Consequence of Malnutrition.
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DOI：
10.1016/j.it.2016.04.003
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发表时间：
2016-06
影响因子：
16.8
通讯作者：
Prendergast AJ
中科院分区：
文献类型：
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作者：
Bourke CD;Berkley JA;Prendergast AJ
营养不良，包括营养不足和营养过剩，是造成全球巨大发病率和死亡率负担的原因。营养不良是营养吸收紊乱的结果，但也以反复感染和慢性炎症为特征，这意味着潜在的免疫缺陷。营养不良的父母在出生前通过免疫表观基因组的改变而出现缺陷，这可能导致营养不良的代际循环。这篇综述总结了最近在实验动物、体外模型和人类队列中进行的重要研究，并提出免疫功能障碍既是营养不良的原因，也是营养不良的后果。关注儿童营养不良，我们强调目前对营养不良中免疫功能障碍的理解差距，以期治疗靶向免疫途径作为降低发病率和死亡率的新手段。营养不良的儿童主要死于常见的感染，而免疫缺陷一贯表现为营养不足和营养过剩。父母营养不良导致婴儿免疫和代谢基因的表观遗传修饰。健康的肠道发育依赖于通过免疫受体对膳食营养素、共生微生物和致病微生物的感知。反复感染、慢性炎症和肠病通过改变肠道结构和功能而加重临床营养不良。免疫细胞激活和全身促炎介质水平在营养不良中增加。营养不良损害DC和单核细胞的免疫启动，并损害效应记忆T细胞功能。免疫功能障碍可直接驱动营养不良的病理过程，包括吸收不良、代谢需求增加、生长激素和HPA轴失调以及对感染的易感性增加。
Malnutrition, which encompasses under- and overnutrition, is responsible for an enormous morbidity and mortality burden globally. Malnutrition results from disordered nutrient assimilation but is also characterized by recurrent infections and chronic inflammation, implying an underlying immune defect. Defects emerge before birth via modifications in the immunoepigenome of malnourished parents, and these may contribute to intergenerational cycles of malnutrition. This review summarizes key recent studies from experimental animals, in vitro models, and human cohorts, and proposes that immune dysfunction is both a cause and a consequence of malnutrition. Focusing on childhood undernutrition, we highlight gaps in current understanding of immune dysfunction in malnutrition, with a view to therapeutically targeting immune pathways as a novel means to reduce morbidity and mortality. Undernourished children principally die of common infections, and immune defects are consistently demonstrated in under- and overnutrition. Parental malnutrition leads to epigenetic modifications of infant immune and metabolic genes. Healthy gut development relies on sensing of dietary nutrients, commensal, and pathogenic microbes via immune receptors. Recurrent infections, chronic inflammation, and enteropathy compound clinical malnutrition by altering gut structure and function. Immune cell activation and systemic proinflammatory mediator levels are increased in malnutrition. Malnutrition impairs immune priming by DC and monocytes, and impairs effector memory T cell function. Immune dysfunction can directly drive pathological processes in malnutrition, including malabsorption, increased metabolic demand, dysregulation of the growth hormone and HPA axes, and greater susceptibility to infection.