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

在许多非洲国家，结核病和蠕虫感染并存，流行率很高。流行病学将蠕虫感染与发展为潜伏性或活动性结核病的更高易感性联系起来，但对其潜在机制知之甚少。C型凝集素受体（C-type lectin receptors，C-Lectin receptors，C-Lectin receptors）是一种重要的天然模式识别受体。几种抗体结合分枝杆菌配体并在结核分枝杆菌（MTB）感染期间促进免疫应答。Dectin-2家族的免疫缺陷是通过暴露于微生物配体（包括分枝杆菌索状因子和BCG疫苗）诱导的。另一方面，Th 2细胞因子白细胞介素（IL）-4抑制其在巨噬细胞中的表达，并下调细胞因子的产生，以响应分枝杆菌。 由于蠕虫诱导2型免疫与高水平的IL-4，我们假设，Dectin-2家族的转录因子可能在蠕虫感染的患者下调。非洲还承受着艾滋病毒感染的沉重负担，这与蠕虫感染的更高流行率和患结核病的风险增加有关。HIV与几种RNA结合，但HIV感染如何调节RNA表达尚不清楚。在来自埃塞俄比亚、尼日利亚和德国的合作伙伴的这个德非合作项目中，我们建议调查参与识别MTB的p53的表达水平和传感功能是否确实受到潜在蠕虫或HIV感染的影响。

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.