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Kwashiorkor 相关免疫抑制的机制:来自人体、小鼠和猪研究的见解。

Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies.

机构信息

Center for Food Animal Health, Department of Animal Sciences, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, United States.

Department of Animal Production, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya.

出版信息

Front Immunol. 2022 May 2;13:826268. doi: 10.3389/fimmu.2022.826268. eCollection 2022.

Abstract

Malnutrition refers to inadequate energy and/or nutrient intake. Malnutrition exhibits a bidirectional relationship with infections whereby malnutrition increases risk of infections that further aggravates malnutrition. Severe malnutrition (SM) is the main cause of secondary immune deficiency and mortality among children in developing countries. SM can manifest as marasmus (non-edematous), observed most often (68.6% of all malnutrition cases), kwashiorkor (edematous), detected in 23.8% of cases, and marasmic kwashiorkor, identified in ~7.6% of SM cases. Marasmus and kwashiorkor occur due to calorie-energy and protein-calorie deficiency (PCD), respectively. Kwashiorkor and marasmic kwashiorkor present with reduced protein levels, protein catabolism rates, and altered levels of micronutrients leading to uncontrolled oxidative stress, exhaustion of anaerobic commensals, and proliferation of pathobionts. Due to these alterations, kwashiorkor children present with profoundly impaired immune function, compromised intestinal barrier, and secondary micronutrient deficiencies. Kwashiorkor-induced alterations contribute to growth stunting and reduced efficacy of oral vaccines. SM is treated with antibiotics and ready-to-use therapeutic foods with variable efficacy. Kwashiorkor has been extensively investigated in gnotobiotic (Gn) mice and piglet models to understand its multiple immediate and long-term effects on children health. Due to numerous physiological and immunological similarities between pigs and humans, pig represents a highly relevant model to study kwashiorkor pathophysiology and immunology. Here we summarize the impact of kwashiorkor on children's health, immunity, and gut functions and review the relevant findings from human and animal studies. We also discuss the reciprocal interactions between PCD and rotavirus-a highly prevalent enteric childhood pathogen due to which pathogenesis and immunity are affected by childhood SM.

摘要

营养不良是指能量和/或营养素摄入不足。营养不良与感染呈双向关系,即营养不良会增加感染的风险,而感染进一步加重营养不良。严重营养不良(SM)是发展中国家儿童继发免疫缺陷和死亡的主要原因。SM 可表现为消瘦(无水肿),最为常见(所有营养不良病例的 68.6%),也可表现为水肿性消瘦(kwashiorkor),占病例的 23.8%,还可表现为消瘦性水肿性消瘦(marasmic kwashiorkor),占 SM 病例的约 7.6%。消瘦和水肿性消瘦分别是由于热量-能量和蛋白质-热量缺乏(PCD)引起的。kwashiorkor 和消瘦性水肿性消瘦表现为蛋白质水平降低、蛋白质分解代谢率升高以及微量营养素水平改变,导致不受控制的氧化应激、无氧共生菌耗竭和病原菌增殖。由于这些改变,kwashiorkor 患儿的免疫功能严重受损,肠道屏障受损,继发微量营养素缺乏。kwashiorkor 引起的改变导致生长迟缓,口服疫苗的效果降低。SM 采用抗生素和即食治疗性食品治疗,但疗效不一。kwashiorkor 在无菌(Gn)小鼠和仔猪模型中进行了广泛研究,以了解其对儿童健康的多种即时和长期影响。由于猪和人类在生理和免疫学上有许多相似之处,猪是研究 kwashiorkor 发病机制和免疫学的高度相关模型。本文总结了 kwashiorkor 对儿童健康、免疫和肠道功能的影响,并综述了来自人类和动物研究的相关发现。我们还讨论了 PCD 和轮状病毒(一种高度流行的儿童肠道病原体)之间的相互作用,轮状病毒的发病机制和免疫受儿童 SM 的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/9108366/1352b649914c/fimmu-13-826268-g001.jpg

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