Adequate Th2-type response associates with restricted bacterial growth in latent mycobacterial infection of zebrafish.
Adequate Th2-type response associates with restricted bacterial growth in latent mycobacterial infection of zebrafish.
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DOI：
10.1371/journal.ppat.1004190
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发表时间：
2014-06
期刊：
影响因子：
6.7
通讯作者：
Parikka M
中科院分区：
文献类型：
--
作者：
Hammarén MM;Oksanen KE;Nisula HM;Luukinen BV;Pesu M;Rämet M;Parikka M
结核病仍然是世界范围内的一个主要健康问题。目前尚不清楚哪种免疫反应能够成功控制和清除结核分枝杆菌。这方面的知识差距反映在无法开发足够的诊断和治疗工具来防治结核病上。我们在成年斑马鱼中使用海洋分枝杆菌感染模型，并利用斑马鱼种群的异质性来解剖适应性免疫反应的特征，其中一些与控制良好的潜伏期或细菌清除有关，而另一些则与进行性感染有关。在转录水平上测量不同亚群间T细胞反应的差异。研究发现，高总T细胞水平通常与较低的细菌负荷以及T辅助2 （Th2）型基因表达特征相关。在较晚的时间点，自发再激活具有明显的症状，其特征是Th2/Th1标记物比例较低，foxp3的大量诱导反映了调节性T细胞的水平。特征性gata3/tbx21有潜力作为分枝杆菌疾病状态的生物标志物。结核病是一种在世界范围内传播的常见且具有潜在致命性的肺部疾病。据估计，世界人口的三分之一感染了结核分枝杆菌，但大多数人发展为潜伏性疾病，并有可能重新激活。一些人被认为能够清除感染。目前的疫苗不能提供足够的保护以预防该病，而且由于不正确使用抗生素，对治疗的耐药性已大大增加。迫切需要新的治疗方法，如调节宿主的免疫反应。然而，针对结核病的理想免疫反应尚不清楚。此外，需要更准确的诊断工具来区分潜伏患者中的高风险个体，以便对最有可能从中受益的人进行治疗。在本研究中，我们使用海洋分枝杆菌-斑马鱼模型来研究分枝杆菌感染时T细胞的反应。利用斑马鱼种群的自然异质性，我们发现疾病严重程度（细菌负荷）与T细胞反应的类型和大小之间存在关联。我们对典型T细胞特征的研究结果是有用的诊断生物标志物，并为基于免疫调节的治疗方法提供了新的理解。
Tuberculosis is still a major health problem worldwide. Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease. Tuberculosis is a common and potentially lethal lung disease spread worldwide. One third of the world's population is estimated to be infected with Mycobacterium tuberculosis, yet most individuals develop a latent disease which has the potential to reactivate. Some are thought to be able to clear the infection. The current vaccine does not give adequate protection against the disease, and due to incorrect use of antibiotics, resistance to treatment has substantially increased. There is an urgent need for novel treatment approaches, such as modulation of the host's immune response. However, the ideal immune response against tuberculosis is unknown. In addition, more accurate diagnostic tools are needed for distinguishing the high risk individuals among latent patients so that treatment could be given to those that are most likely to benefit from it. In this study, we used the Mycobacterium marinum-zebrafish model to study the T cell responses in mycobacterial infection. Utilizing the natural heterogeneity of the zebrafish population, we found associations between the disease severity (bacterial load) and the type and magnitude of T cell responses. Our results on typical T cell signatures are useful as diagnostic biomarkers as well as provide new understanding needed for therapeutic approaches based on immunomodulation.
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影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1073/pnas.1000494107
发表时间：
2010-09-07
影响因子：
11.1
作者：
Lugo-Villarino, Geanncarlo;Balla, Keir M.;Traver, David
通讯作者：
Traver, David
影响因子：
6.7
作者：
Parikka M;Hammarén MM;Harjula SK;Halfpenny NJ;Oksanen KE;Lahtinen MJ;Pajula ET;Iivanainen A;Pesu M;Rämet M
通讯作者：
Rämet M
T细胞亚群在小鼠中的肺结核感染的免疫和免疫病理学中的相对重要性。
影响因子：
15.3
作者：
Mogues, T;Goodrich, M E;Ryan, L;LaCourse, R;North, R J
通讯作者：
North, R J
影响因子：
32.4
作者：
Hawkins, R. David;Larjo, Antti;Lahesmaa, Riitta
通讯作者：
Lahesmaa, Riitta