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儿童结核病的不同临床结局:一项利用暴露于气溶胶的幼年猕猴的研究

Distinct clinical outcomes in pediatric tuberculosis: A study utilizing infant macaques exposed to aerosol .

作者信息

Turnbull Katherine, Vincent Eunice, Xu Huanbin, Didier Peter J, Blair Robert V, Doyle-Meyers Lara A, Roy Chad J, Mehra Smriti, Kaushal Deepak, Veazey Ronald S, Wang Xiaolei

机构信息

Tulane National Primate Research Center (TNPRC), Covington, LA 70433, USA.

Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.

出版信息

iScience. 2025 Jun 13;28(7):112899. doi: 10.1016/j.isci.2025.112899. eCollection 2025 Jul 18.


DOI:10.1016/j.isci.2025.112899
PMID:40678510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12270685/
Abstract

Clinically relevant pediatric animal models are required to advance research and therapies for () infections in children. Utilizing infant rhesus macaques exposed to controlled doses of aerosolized CDC1551, we systematically monitored physical changes and assessed signs of tuberculosis, including physical examinations, clinical blood chemistry, radiography, and histopathology. Our results demonstrated that infant macaques exposed a physiologically relevant, low dose of aerosolized CDC1551 and exhibited immune control of infection similar to that observed in human infants, while those exposed to a higher dose experienced widespread dissemination, rapid disease progression, and mortality within six weeks after exposure. These findings suggest that pediatric rhesus macaques exposed to a low dose of via the aerosol route could serve as a translational model for natural infection in children, thereby allowing for the recapitulation of the immunopathogenesis and treatment of pediatric tuberculosis in a clinical setting.

摘要

需要有临床相关的儿科动物模型来推进针对儿童()感染的研究和治疗。利用暴露于可控剂量雾化的CDC1551的幼龄恒河猴,我们系统地监测了身体变化并评估了结核病的体征,包括体格检查、临床血液化学、放射学和组织病理学。我们的结果表明,暴露于生理相关低剂量雾化CDC1551的幼龄猕猴表现出与人类婴儿相似的感染免疫控制,而暴露于高剂量的猕猴在暴露后六周内出现广泛播散、疾病快速进展和死亡。这些发现表明,通过气溶胶途径暴露于低剂量()的儿科恒河猴可作为儿童自然()感染的转化模型,从而能够在临床环境中重现儿科结核病的免疫发病机制并进行治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/1f6ad9e3cba3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/93d49c865cd8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/245544670596/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/acd0b5cd0cf5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/50da31f5836c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/5989535fe701/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/1f6ad9e3cba3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/93d49c865cd8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/245544670596/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/acd0b5cd0cf5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/50da31f5836c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/5989535fe701/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bf/12270685/1f6ad9e3cba3/gr5.jpg

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本文引用的文献

[1]
The Long-Term Impact of Early-Life Tuberculosis Disease on Child Health: A Prospective Birth Cohort Study.

Am J Respir Crit Care Med. 2023-4-15

[2]
WHO's Global Tuberculosis Report 2022.

Lancet Microbe. 2023-1

[3]
Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management.

Front Cell Infect Microbiol. 2022

[4]
Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs.

J Clin Invest. 2022-9-15

[5]
Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.

Immunity. 2022-5-10

[6]
Tuberculosis Infection in Children and Adolescents: Testing and Treatment.

Pediatrics. 2021-12-1

[7]
Abnormal Tryptophan Metabolism in HIV and Infection.

Front Microbiol. 2021-6-28

[8]
Tuberculosis: The Past, the Present and the Future.

Respiration. 2021

[9]
Immunological Aspects of Diagnosis and Management of Childhood Tuberculosis.

Infect Drug Resist. 2021-3-8

[10]
The knowns and unknowns of latent Mycobacterium tuberculosis infection.

J Clin Invest. 2021-2-1

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