The eosinophil: Anti-parasite effector cell or mediator of pathology?

嗜酸性粒细胞：抗寄生虫效应细胞还是病理介质？

• 批准号: BB/D013550/1
• 负责人: Rachel Lawrence
• 金额: $ 38.33万
• 依托单位: Royal Veterinary College
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD013550%2F1
• 关键词: eosinophil; Anti; parasite; effector; cell

Parasites can live relatively quietly in their hosts or they can cause excessive tissue damage which seriously affects the life of the infected individual. This project will study a particular cell type, the eosinophil, which appears to be capable of either curing the individual of disease or of causing harmful tissue reactions. Millions of people and animals in the world are infected by parasitic nematode worms. These parasites occupy a multitude of different sites within the body, from the gut to the skin or blood. The damage that worms cause varies between different parasite species and also between different infected individuals. Some individuals are relatively resistant to infection with worms, while others, are particularly susceptible. Resistance to parasitic nematode disease depends on the immune responses that the body develops to fight these infections. Interestingly, in many infections, although a specific type of immune response can kill parasitic worms, that particular immune response may also be guilty of damaging the tissues of the host organism. Therefore in areas of the world where individuals are continually at risk of infection with parasitic worms, the immune response can be viewed as a finely/balanced see-saw that rocks between the ability to kill parasites and the ability of the response to cause harm. As researchers, we wish to find out the triggers that push the see-saw in one direction or the other and the controls that the body puts in place to prevent the balance from being biased too strongly in one or other direction. We have identified a particular cell-type, the eosinophil, that appears to be important in parasite-killing but when over-active it is also involved in tissue damage. Our aim in this research is to definitively establish, once and for all, that this cell type, the eosinophil, is capable of killing parasites and of damaging tissues. We will then establish the biological factors that are produced by eosinophils in both of these situations to try and define whether there are differences between esoinophils that kill parasites and those that cause damage. Lastly we will try to identify particular immune responses that limit the damage caused by eosinophils. This work is particularly exciting because it is only recently that scientists have developed the technological tools that will help us to identify the role played by eosinophils. In addition, immune responses to parasitic worms are remarkably similar to the immune responses that cause asthma, therefore the results of our studies will be useful both for fighting infections with worms and for fighting the symptoms of asthma.

寄生虫可以相对安静地生活在宿主体内，或者它们可以造成严重影响受感染个体生命的过度组织损伤。这个项目将研究一种特殊的细胞类型，嗜酸性粒细胞，它似乎能够治愈疾病的个体或引起有害的组织反应。世界上数以百万计的人和动物受到寄生蠕虫感染。这些寄生虫占据身体内的许多不同部位，从肠道到皮肤或血液。蠕虫造成的损害在不同的寄生虫物种之间以及在不同的感染个体之间都有所不同。有些个体对蠕虫感染具有相对抵抗力，而另一些个体则特别敏感。对寄生线虫病的抵抗力取决于身体为对抗这些感染而产生的免疫反应。有趣的是，在许多感染中，尽管特定类型的免疫反应可以杀死寄生蠕虫，但这种特定的免疫反应也可能损害宿主生物体的组织。因此，在世界上个人持续处于寄生蠕虫风险的地区，免疫应答可以被视为在杀死寄生虫的能力和引起伤害的应答能力之间摇摆的精细/平衡的跷跷板。作为研究人员，我们希望找出将跷跷板推向一个方向或另一个方向的触发因素，以及身体为防止平衡过于偏向一个方向或另一个方向而设置的控制措施。我们已经确定了一种特殊的细胞类型，嗜酸性粒细胞，这似乎是重要的寄生虫杀死，但当过度活跃，它也参与组织损伤。我们这项研究的目的是一劳永逸地确定这种细胞类型，嗜酸性粒细胞，能够杀死寄生虫和破坏组织。然后，我们将确定嗜酸性粒细胞在这两种情况下产生的生物学因素，以试图确定杀死寄生虫的嗜酸性粒细胞和造成损害的嗜酸性粒细胞之间是否存在差异。最后，我们将试图确定特定的免疫反应，限制嗜酸性粒细胞造成的损害。这项工作特别令人兴奋，因为直到最近科学家才开发出技术工具，帮助我们确定嗜酸性粒细胞所起的作用。此外，对寄生虫的免疫反应与引起哮喘的免疫反应非常相似，因此我们的研究结果将有助于对抗蠕虫感染和对抗哮喘症状。

项目成果

Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

• DOI: 10.1371/journal.pbio.1000525
• 发表时间: 2010-10-19
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Babayan SA;Read AF;Lawrence RA;Bain O;Allen JE
• 通讯作者: Allen JE

Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis.

• DOI: 10.1016/j.immuni.2016.03.003
• 发表时间: 2016-04-19
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Matthews SP;McMillan SJ;Colbert JD;Lawrence RA;Watts C
• 通讯作者: Watts C

Eosinophils are important for protection, immunoregulation and pathology during infection with nematode microfilariae.

• DOI: 10.1371/journal.ppat.1003988
• 发表时间: 2014-03
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Cadman ET;Thysse KA;Bearder S;Cheung AY;Johnston AC;Lee JJ;Lawrence RA
• 通讯作者: Lawrence RA

Decreased nematode clearance and anti-phosphorylcholine-specific IgM responses in mannose-binding lectin-deficient mice

• DOI: 10.1111/imcb.12219
• 发表时间: 2019-03-01
• 期刊: IMMUNOLOGY AND CELL BIOLOGY
• 影响因子: 4
• 作者: Ahmed，Rubina;Cadman，Emma T.;Lawrence，Rachel A.
• 通讯作者: Lawrence，Rachel A.