Modulation of C-type lectin receptor expression by helminth or HIV infection: setting the threshold for sensing of mycobacteria?

蠕虫或 HIV 感染对 C 型凝集素受体表达的调节：设定分枝杆菌传感的阈值？

• 批准号: 405489036
• 负责人: Professor Dr. Roland Lang
• 金额: --
• 依托单位: Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/405489036?language=en
• 关键词: Modulation; type; lectin; receptor; expression

Tuberculosis (TB) and helminth infections are coexisting and highly prevalent in many African countries. Epidemiology links helminth infections with higher susceptibility to develop latent or active TB, but the underlying mechanisms are poorly understood. C-type lectin receptors (CLR) are important innate pattern recognition receptors for sensing of microbial carbohydrate and glycolipid ligands. Several CLR bind mycobacterial ligands and contribute to the immune response during infection with Mycobacterium tuberculosis (MTB). CLR of the Dectin-2 family are induced by exposure to microbial ligands, including mycobacterial cord factor and the BCG vaccine. On the other hand, the Th2 cytokine interleukin (IL)-4 inhibits their expression in macrophages and down-regulates cytokine production in response to mycobacteria. Since helminths induce type 2 immunity with high levels of IL-4, we hypothesize that Dectin-2 family CLR may be down-regulated in worm-infected patients. Africa also carries a high burden of HIV infection, which is associated with higher prevalence of helminth-infection and increased risk to develop TB. HIV is bound by several CLR, but how HIV infection regulates CLR expression is unknown. In this German-African cooperation project of partners from Ethiopia, Nigeria and Germany, we propose to investigate whether expression levels and sensing function of CLR involved in recognition of MTB are indeed affected by underlying helminth- or HIV-infection.

在许多非洲国家，结核病和寄生虫感染共存并高度流行。流行病学将寄生虫感染与发展为潜伏性或活动性结核病的较高易感性联系起来，但其潜在机制尚不清楚。c型凝集素受体（CLR）是一种重要的天然模式识别受体，用于感知微生物碳水化合物和糖脂配体。几种CLR结合分枝杆菌配体，并在感染结核分枝杆菌（MTB）期间促进免疫反应。Dectin-2家族的CLR是由暴露于微生物配体（包括脊髓分枝杆菌因子和卡介苗）诱导的。另一方面，Th2细胞因子白细胞介素(IL)-4抑制其在巨噬细胞中的表达，下调分枝杆菌对细胞因子的产生。由于蠕虫诱导高水平IL-4的2型免疫，我们假设Dectin-2家族CLR可能在蠕虫感染患者中下调。非洲也是艾滋病毒感染的高负担地区，这与较高的蠕虫感染流行率和发展为结核病的风险增加有关。HIV与几种CLR结合，但HIV感染如何调节CLR表达尚不清楚。在这个由来自埃塞俄比亚、尼日利亚和德国的合作伙伴组成的德非合作项目中，我们提议研究参与MTB识别的CLR的表达水平和感知功能是否确实受到潜在的蠕虫或hiv感染的影响。