TGF-beta activation by gut dendritic cells: identifying a critical pathway in regulation of chronic parasitic infection

我们的免疫系统的功能是检测和摧毁进入人体的有害病原体。一旦感染，免疫反应迅速激活，以确保尽快处理威胁。然而，被称为蠕虫寄生虫的病原体可以劫持免疫系统来抑制旨在消除感染的反应，因此允许病原体在体内生存和繁殖。这些所谓的慢性蠕虫感染是主要的世界健康问题，超过四分之一的世界人口受到影响，大多数在发展中国家。蠕虫寄生虫感染会引起严重的健康和经济问题，但目前对感染的治疗非常有限。因此，科学研究的一个重要领域旨在了解蠕虫如何控制免疫反应，使它们在我们体内生存。因此，这些工作将导致确定潜在的新的治疗目标，用于治疗慢性蠕虫感染。我们的新的令人兴奋的数据已经确定了重要的分子，在慢性蠕虫感染的发展至关重要。因此，当称为树突状细胞的免疫系统细胞激活称为TGF β的重要分子的能力降低时，慢性感染不能在重要的人类肠道蠕虫感染的小鼠模型中发展。然而，为什么发生慢性感染的保护是完全未知的。本文提出的工作旨在揭示为什么免疫系统中缺乏特定途径会导致肠道慢性感染的完全保护，确定参与这种保护的免疫系统细胞和分子。我们还将确定这种对感染的抵抗力是否见于其他类型的寄生虫，或者保护是否特异于感染肠道的蠕虫寄生虫。因此，我们的工作将提供重要的见解免疫分子，细胞和机制，参与允许寄生虫发展慢性感染，从而确定潜在的新的治疗目标，用于治疗这些毁灭性的疾病。

Our immune system functions to detect and destroy harmful pathogens that enter the body. Upon infection, immune responses are rapidly activated, to ensure the threat is dealt with as quickly as possible. However, pathogens known as helminth parasites can hijack the immune system to suppress responses aimed at eliminating the infection, therefore allowing the pathogen to live and breed inside the body. These so-called chronic helminth infections are major world health problems, with over one quarter of the world population affected, mostly in developing countries. Infections with helminth parasites cause major health and economic problems, but at present treatments for the infections are extremely limited. A vital area of scientific research therefore aims to understand how helminths control immune responses to allow their survival inside our body. Such work will therefore lead to the identification of potential novel therapeutic targets for treating chronic helminth infection.Our new exciting data has identified important molecules that are critically involved in the development of chronic helminth infection. Hence, when cells of the immune system called dendritic cells have reduced ability to activate an important molecule called TGFbeta, chronic infection cannot develop in a mouse model of an important human gut helminth infection. However, why protection from chronic infection occurs is completely unknown. The work proposed here aims to uncover why lack of a specific pathway in the immune system causes complete protection from chronic infection in the gut, determining the cells and molecules of the immune system involved in such protection. We will also determine whether such resistance from infection is seen for other types of parasites, or whether protection is specific to helminth parasites that infect the gut. Our work will therefore provide important insights into immune molecules, cells and mechanisms that are involved in allowing parasites to develop chronic infection, thus identifying potential novel therapeutic targets for treatment of these devastating diseases.