T. gondii infection induces IL-1R dependent chronic cachexia and perivascular fibrosis in the liver and skeletal muscle.
T. gondii infection induces IL-1R dependent chronic cachexia and perivascular fibrosis in the liver and skeletal muscle.
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DOI：
10.1038/s41598-020-72767-0
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发表时间：
2020-09-24
影响因子：
4.6
通讯作者：
Ewald SE
中科院分区：
文献类型：
--
作者：
Melchor SJ;Hatter JA;Castillo ÉAL;Saunders CM;Byrnes KA;Sanders I;Abebayehu D;Barker TH;Ewald SE
恶病质是一种进行性肌肉消耗性疾病，在多种慢性疾病中导致死亡。目前，恶病质领域缺乏概括临床疾病的长期动力学的动物模型，这将提供对慢性恶病质的病理生理学的深入了解和测试疾病逆转的治疗方法的工具。弓形虫（T.弓形虫）是一种利用保守机制感染啮齿动物和人类宿主的原生动物寄生虫。感染是终身的，并且与小鼠的慢性体重减轻和肌肉萎缩有关。我们最近证明了T. Gondii诱导的肌肉萎缩符合恶病质的临床定义。在这里，T. Gondii诱导的慢性恶病质模型显示，恶病质小鼠在感染后9周在主要代谢器官（包括脂肪组织、骨骼肌和肝脏）中发生血管周围纤维化。恶病质以及肝和骨骼肌纤维化的发展依赖于通过I型IL-1 R受体的完整信号传导。IL-1α在体外足以激活培养的成纤维细胞和原代肝星状细胞（肝脏中的肌成纤维细胞前体），并且IL-1α在恶病质患者血清和肝脏中升高，提示慢性IL-1 R信号传导可能导致恶病质相关纤维化的机制。
Cachexia is a progressive muscle wasting disease that contributes to death in a wide range of chronic diseases. Currently, the cachexia field lacks animal models that recapitulate the long-term kinetics of clinical disease, which would provide insight into the pathophysiology of chronic cachexia and a tool to test therapeutics for disease reversal. Toxoplasma gondii (T. gondii) is a protozoan parasite that uses conserved mechanisms to infect rodents and human hosts. Infection is lifelong and has been associated with chronic weight loss and muscle atrophy in mice. We have recently shown that T. gondii-induced muscle atrophy meets the clinical definition of cachexia. Here, the longevity of the T. gondii-induced chronic cachexia model revealed that cachectic mice develop perivascular fibrosis in major metabolic organs, including the adipose tissue, skeletal muscle, and liver by 9 weeks post-infection. Development of cachexia, as well as liver and skeletal muscle fibrosis, is dependent on intact signaling through the type I IL-1R receptor. IL-1α is sufficient to activate cultured fibroblasts and primary hepatic stellate cells (myofibroblast precursors in the liver) in vitro, and IL-1α is elevated in the sera and liver of cachectic, suggesting a mechanism by which chronic IL-1R signaling could be leading to cachexia-associated fibrosis.
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DOI：
10.1084/jem.20111020
发表时间：
2011-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Braun TP;Zhu X;Szumowski M;Scott GD;Grossberg AJ;Levasseur PR;Graham K;Khan S;Damaraju S;Colmers WF;Baracos VE;Marks DL
通讯作者：
Marks DL
影响因子：
30.3
作者：
Benson A;Pifer R;Behrendt CL;Hooper LV;Yarovinsky F
通讯作者：
Yarovinsky F
影响因子：
3.2
作者：
Atmaca HT;Gazyagcı AN;Canpolat S;Kul O
通讯作者：
Kul O
影响因子：
3.5
作者：
Filippatos, GS;Kanatselos, C;Uhal, B
通讯作者：
Uhal, B
DOI：
10.1152/ajpendo.1998.274.3.e439
发表时间：
1998-03-01
影响因子：
5.1
作者：
Arsenijevic, D;Girardier, L;Dulloo, AG
通讯作者：
Dulloo, AG