Analysis of pathomechanisms of immune reconstitution inflammatory syndrome in Cryptococcus neoformans-infected mice

新型隐球菌感染小鼠免疫重建炎症综合征发病机制分析

• 批准号: 221792892
• 负责人: Professor Dr. Gottfried Alber
• 金额: --
• 依托单位: Institut für Immunologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/221792892?language=en
• 关键词: Analysis; pathomechanisms; immune; reconstitution; inflammatory

Antiretroviral therapy (ART) has yielded major advances in fighting the HIV pandemic. However, a significant medical problem remains to be solved in a number of HIV+ patients co-infected with Cryptococcus neoformans. Upon ART-induced restoration of the immune system this subgroup of patients develops a life-threatening immune reconstitution inflammatory syndrome (IRIS). The mechanisms of the uncontrolled inflammatory response during cryptococcal IRIS are enigmatic. Thus, we recently established a mouse model of cryptococcal IRIS to study disease development. Initial data point to a central role of T helper cells in pathogenesis. The objective of this application is to further refine our model and study the cellular and molecular players of cryptococcal IRIS in depth. The project should result in novel ways to diagnose and predict cryptococcal IRIS. Moreover, targets will be identified for novel therapies which can be tested in this murine model. Together, the proposed study will enable insights in the regulatory mechanisms of inflammatory responses in the immunodeficient as well as immune reconstituting organism.

抗逆转录病毒疗法在防治艾滋病毒流行病方面取得了重大进展。然而，许多HIV阳性患者合并新型隐球菌感染仍有一个重要的医学问题有待解决。在art诱导的免疫系统恢复后，这一亚群患者发展为危及生命的免疫重建炎症综合征（IRIS）。隐球菌性IRIS期间不受控制的炎症反应机制尚不清楚。因此，我们最近建立了隐球菌性IRIS小鼠模型来研究疾病的发展。初步数据表明辅助性T细胞在发病机制中起核心作用。本应用程序的目的是进一步完善我们的模型，并深入研究隐球菌IRIS的细胞和分子参与者。该项目将产生诊断和预测隐球菌IRIS的新方法。此外，靶点将被确定为新的治疗方法，可以在这种小鼠模型中进行测试。总之，提出的研究将使免疫缺陷和免疫重建生物体的炎症反应的调节机制的见解。