Characterization of Leishmania-Specific T cells in human skin and blood during cutaneous and mucocutaneous leishmaniasis

皮肤和粘膜皮肤利什曼病期间人体皮肤和血液中利什曼原虫特异性 T 细胞的表征

• 批准号: MR/N017749/1
• 负责人: Arne Akbar
• 金额: $ 14.85万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN017749%2F1
• 关键词: Characterization; Leishmania; Specific; cells; human

Parasites belonging to the genus Leishmania are among the most diverse of human pathogens, both in terms of geographical distribution and in the variety of clinical syndromes caused by them. Currently, 12 million people are infected worldwide in 88 tropical/subtropical countries, 2 million new infections are reported annually, and 350 million people are under infection risk. In the past decade, the number of cases in endemic areas has increased sharply. In addition, leishmaniasis is spreading to several non-endemic areas of the world due to coinfections with HIV. Control measures currently available are case detection and treatment with drugs, which are expensive, not always available and cannot be self-administered. The problem is further aggravated by the surge of drug resistance parasites necessitating the development of an anti-Leishmania vaccine or other immunological therapies urgent. Research has demonstrated the importance of the immunity in controlling both cutaneous and mucocotaneous leishmaniasis, however the majority of this work has been performed on blood samples taken from patients and not from the site of infection at the skin. In this context, the current project aims to characterize the immune mechanisms involved in controlling Leishmania in both the blood and the skin. In this proposal, we aim to apply this established approach for the first time in studies with human localized cutaneous (LCL) and mucocutaneous leishmaniasis (MCL) in order to understand the immune mechanisms associated to cell development, function and regulation in the skin and blood. Through this work we will be able to identify in detail components of the cutaneous and systemic immunity that are involved during infection and determine which of these factor can drive lesion development or/and parasite control. The results will also provide important data that will increase the understanding of Leishmania immunity providing explanations about pathological differences observed in cutaneous and mucocotaneous leishmaniasis patients and contribute to the improved design of future vaccines and drug target.

属于利什曼原虫属的寄生虫是人类病原体中最多样化的，无论是在地理分布方面还是在由它们引起的各种临床综合征方面。目前，全世界88个热带/亚热带国家有1 200万人感染，每年报告200万新感染病例，3.5亿人面临感染风险。在过去十年中，流行地区的病例数量急剧增加。此外，由于与艾滋病毒合并感染，利什曼病正在向世界上几个非流行地区蔓延。目前可用的控制措施是病例检测和药物治疗，但费用昂贵，并非总是可用，而且不能自我管理。抗药性寄生虫的激增使问题进一步恶化，迫切需要开发抗利什曼原虫疫苗或其他免疫疗法。研究已经证明了免疫力在控制皮肤和粘膜利什曼病中的重要性，然而，这项工作的大部分是在从患者身上采集的血液样本上进行的，而不是从皮肤感染部位采集的。在这种情况下，目前的项目旨在描述参与控制血液和皮肤中利什曼原虫的免疫机制。在这项提案中，我们的目标是首次将这种既定的方法应用于人类局部皮肤（LCL）和皮肤粘膜利什曼病（MCL）的研究，以了解与皮肤和血液中细胞发育，功能和调节相关的免疫机制。通过这项工作，我们将能够详细识别感染过程中涉及的皮肤和全身免疫的组成部分，并确定这些因素中的哪一个可以驱动病变发展或/和寄生虫控制。这些结果还将提供重要的数据，增加对利什曼原虫免疫的理解，解释在皮肤和粘膜利什曼病患者中观察到的病理差异，并有助于改进未来疫苗和药物靶点的设计。

项目成果

Convergence of Innate and Adaptive Immunity during Human Aging.

• DOI: 10.3389/fimmu.2016.00445
• 发表时间: 2016
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Pereira BI;Akbar AN
• 通讯作者: Akbar AN

Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5'-Monophosphate-Activated Protein Kinase.

• DOI: 10.4049/jimmunol.1600590
• 发表时间: 2016-10-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Müller-Durovic B;Lanna A;Covre LP;Mills RS;Henson SM;Akbar AN
• 通讯作者: Akbar AN

Circulating Senescent T Cells Are Linked to Systemic Inflammation and Lesion Size During Human Cutaneous Leishmaniasis

• DOI: 10.3389/fimmu.2018.03001
• 发表时间: 2019-01-04
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: Covre, Luciana P.;Martins, Regia F.;Gomes, Daniel C. O.
• 通讯作者: Gomes, Daniel C. O.

A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging.

• DOI: 10.1038/ni.3665
• 发表时间: 2017-03
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Lanna A;Gomes DC;Muller-Durovic B;McDonnell T;Escors D;Gilroy DW;Lee JH;Karin M;Akbar AN
• 通讯作者: Akbar AN

Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation.

通过阻断p38促丝分裂原激活蛋白（MAP）激酶诱导的炎症，增强皮肤免疫力。

• DOI: 10.1016/j.jaci.2017.10.032
• 发表时间: 2018-09
• 期刊: The Journal of allergy and clinical immunology
• 作者: Vukmanovic-Stejic M;Chambers ES;Suárez-Fariñas M;Sandhu D;Fuentes-Duculan J;Patel N;Agius E;Lacy KE;Turner CT;Larbi A;Birault V;Noursadeghi M;Mabbott NA;Rustin MHA;Krueger JG;Akbar AN
• 通讯作者: Akbar AN