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Fungi on the Brain: Interrogating Host-Pathogen Interactions during Fungal Meningitis

大脑中的真菌：探究真菌性脑膜炎期间宿主与病原体的相互作用

基本信息

批准号：
MR/S024611/1
负责人：
Rebecca Drummond
金额：
$ 150.43万
依托单位：
University of Birmingham
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FS024611%2F1
关键词：
Fungi Brain Interrogating Host Pathogen

项目摘要

Fungi are a major cause of ill-health in humans; hundreds of millions of people suffer from skin and mucosal fungal infections every year, while life-threatening invasive fungal infections cause more deaths around the world than malaria and some types of cancer. These life-threatening invasive fungal infections are a particular cause for concern, because we have limited antifungal drugs to treat them, diagnosis is very difficult and there are no fungal vaccines. Knowledge of how protective immune responses against fungi are controlled can help us to design vaccines and immune-based treatments for these infections. Yet, compared to bacteria and viruses, fungi are poorly studied and only a few research groups in the world have the expertise to understand how the immune system deals with fungi. Fungal infection of the brain and central nervous system (meningitis) is the most lethal form of invasive fungal disease. The most common fungal brain infection is cryptococcal meningitis, caused by the fungus Cryptococcus neoformans, which mostly affects people with weakened immune systems in low and middle-income countries in sub-Saharan Africa. Cryptococcal meningitis is not easily treated; 4 out of every 5 patients with this disease die from it. New treatment strategies and diagnostics are therefore urgently needed, which in turn could potentially improve the social and economic performance of these low/middle-income countries by improving the population's health. The goal of my research is to better understand immunity to Cryptococcus specifically in the brain. Each organ has its own specialised immune cells that are involved in surveillance and alarming other cells of the immune system to the presence of an invader. Microglia are the specialised cells of the brain's internal immune system. We've known about them for a long time but they are still mysterious since, until recently, we didn't have the tools needed to understand them. These new tools include animal models that enable us to delete microglia from the brain so we can determine how the absence of microglia affects disease progression and resolution. Using my background in fungal immunology and microglia biology, I have adapted these microglia-depleting mice with animal models of fungal infection to allow me to understand what microglia do when confronted with a fungal invader. Answering this fundamental question will then help us to determine what treatments will work best for fungal CNS infection so we can reduce the impact of this devastating disease on human health.

真菌是人类健康不良的主要原因；每年有数亿人遭受皮肤和粘膜真菌感染，而危及生命的侵袭性真菌感染在全世界造成的死亡人数比疟疾和某些类型的癌症还要多。这些危及生命的侵袭性真菌感染尤其值得关注，因为我们治疗它们的抗真菌药物有限，诊断非常困难，而且没有真菌疫苗。了解如何控制针对真菌的保护性免疫反应可以帮助我们设计针对这些感染的疫苗和基于免疫的治疗方法。然而，与细菌和病毒相比，真菌的研究很少，世界上只有少数研究小组拥有了解免疫系统如何处理真菌的专业知识。大脑和中枢神经系统的真菌感染（脑膜炎）是侵袭性真菌病中最致命的形式。最常见的真菌性脑部感染是隐球菌性脑膜炎，由新型隐球菌引起，主要影响撒哈拉以南非洲低收入和中等收入国家免疫系统较弱的人群。隐球菌性脑膜炎不易治疗；每 5 名患有这种疾病的患者中就有 4 人死于该病。因此，迫切需要新的治疗策略和诊断方法，这反过来又可能通过改善人口健康来改善这些低/中等收入国家的社会和经济表现。我的研究目标是更好地了解对隐球菌的免疫力，特别是大脑中的免疫力。每个器官都有自己专门的免疫细胞，这些细胞参与监视并警告免疫系统的其他细胞入侵者的存在。小胶质细胞是大脑内部免疫系统的特殊细胞。我们已经了解它们很长时间了，但它们仍然很神秘，因为直到最近，我们还没有理解它们所需的工具。这些新工具包括动物模型，使我们能够从大脑中删除小胶质细胞，这样我们就可以确定小胶质细胞的缺失如何影响疾病的进展和解决。利用我在真菌免疫学和小胶质细胞生物学方面的背景，我用真菌感染的动物模型改造了这些小胶质细胞耗尽的小鼠，使我能够了解小胶质细胞在面对真菌入侵者时会做什么。回答这个基本问题将有助于我们确定哪种治疗方法最适合治疗中枢神经系统真菌感染，从而减少这种毁灭性疾病对人类健康的影响。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Molecular and Microscopic Methods of Quantifying Candida albicans Cell Wall PAMP Exposure.

定量白色念珠菌细胞壁 PAMP 暴露的分子和显微镜方法。

DOI：
10.1007/978-1-0716-2549-1_23
发表时间：
2022
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Bojang E
通讯作者：
Bojang E

Sowing the seeds of infection.

播下感染的种子。

DOI：
10.1016/j.chom.2022.09.008
发表时间：
2022
期刊：
Cell host & microbe
影响因子：
30.3
作者：
Ballou ER
通讯作者：
Ballou ER

Microglia protect fungi against copper starvation and promote brain infection

DOI：
10.1101/2022.09.07.506901
发表时间：
2022-09
期刊：
bioRxiv
影响因子：
0
作者：
Sally H. Mohamed;M. Fu;Sofia Hain;Alanoud Alselami;E. Vanhoffelen;Yanjian Li;E. Bojang;R. Lukande-R.
通讯作者：
Sally H. Mohamed;M. Fu;Sofia Hain;Alanoud Alselami;E. Vanhoffelen;Yanjian Li;E. Bojang;R. Lukande-R.

settings Open AccessReview The Diverse Roles of Monocytes in Cryptococcosis

设置开放访问回顾单核细胞在隐球菌病中的多种作用