Adipose Tissue Regulates Pulmonary Pathology during TB Infection
Adipose Tissue Regulates Pulmonary Pathology during TB Infection
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DOI：
10.1128/mbio.02771-18
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发表时间：
2019-03-01
期刊：
影响因子：
6.4
通讯作者：
Nagajyothi, Jyothi F.
中科院分区：
文献类型：
--
作者：
Ayyappan, Janeesh Plakkal;Ganapathi, Usha;Nagajyothi, Jyothi F.
结核病 (TB) 由结核分枝杆菌感染引起，仍然是全世界死亡和发病的主要原因。世界上三分之一的人口感染了结核分枝杆菌，美国约有 1500 万潜伏性结核感染 (LTBI) 患者。据估计，10% 的 LTBI 患者有进展为活动性疾病的风险。体重减轻或消瘦，伴随着体脂显着减少，通常与活动性结核病有关，并被认为具有免疫抑制作用，是疾病严重程度和结果的主要决定因素。虽然肺部是结核分枝杆菌感染和结核病表现的主要部位，但最近的报告表明，脂肪组织是结核分枝杆菌的重要储存库。在本文中，我们使用转基因诱导型“无脂肪”模型系统 FAT-ATTAC（通过靶向激活 caspase 8 进行脂肪凋亡）小鼠，研究了结核分枝杆菌感染、脂肪组织和结核病进展之间的关联。通过在结核分枝杆菌感染期间选择性消融脂肪组织，我们直接测试了脂肪细胞损失和脂肪组织生理学在调节肺部病理、细菌负荷和免疫状态中的作用。我们的结果证实了小鼠气溶胶感染后脂肪组织中存在结核分枝杆菌，并表明脂肪细胞的损失与肺结核分枝杆菌负荷和病理的增加有关。我们的结论是，LTBI 期间脂肪组织的急性损失可能使宿主易患活动性结核病。 重要性 尽管肺部是结核病表现的入口和主要部位，但我们和其他人已经证明，结核分枝杆菌也持续存在于气溶胶感染动物的脂肪组织中，并直接或间接改变脂肪组织生理学，从而改变全身 免疫代谢稳态。我们目前的报告表明，脂肪细胞（脂肪细胞）的损失对促进结核病期间肺部发病机制的严重程度产生直接影响，增进了我们对消耗与结核病激活/再激活之间致病相互作用的理解。
Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of individuals with LTBI are at risk of progressing to active disease. Loss of body mass, or wasting, accompanied by a significant reduction of body fat is often associated with active TB disease and is considered to be immunosuppressive and a major determinant of severity and outcome of disease. While the lungs are the primary site of M. tuberculosis infection and TB manifestation, recent reports have shown that adipose tissue serves as an important reservoir for M. tuberculosis. In this article, we investigated the association between M. tuberculosis infection, adipose tissue, and TB disease progression using a transgenic inducible "fatless" model system, the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) mouse. By selectively ablating fat tissue during M. tuberculosis infection, we directly tested the role of fat cell loss and adipose tissue physiology in regulating pulmonary pathology, bacterial burden, and immune status. Our results confirm the presence of M. tuberculosis in fat tissue after aerosol infection of mice and show that loss of fat cells is associated with an increase in pulmonary M. tuberculosis burden and pathology. We conclude that acute loss of adipose tissue during LTBI may predispose the host to active TB disease.IMPORTANCE Although the lungs are the port of entry and the predominant site of TB disease manifestation, we and others have demonstrated that M. tuberculosis also persists in adipose tissue of aerosol-infected animals and directly or indirectly alters adipose tissue physiology, which in turn alters whole-body immuno-metabolic homeostasis. Our present report demonstrates a direct effect of loss of adipocytes (fat cells) on promoting the severity of pulmonary pathogenesis during TB, advancing our understanding of the pathogenic interactions between wasting and TB activation/reactivation.