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寄生虫，无论是在地理分布和由其引起的临床综合症的种类方面。目前，在88个热带/亚热带国家中，全世界有1,200万人被感染，每年有200万新的感染，3.5亿人受感染风险。在过去的十年中，地方性地区的案件数量急剧增加。此外，由于与艾滋病毒的共同感染，利什曼病正在扩散到世界上几个非流行地区。当前可用的控制措施是用药物检测和治疗，这些药物很昂贵，并不总是可用，不能自我管理。耐药性寄生虫的激增需要开发抗leishmania疫苗或其他免疫疗法，这进一步加剧了问题。研究表明，免疫力在控制皮肤和毛发透明的利什曼病中的重要性，但是这项工作的大部分是对从患者而不是从皮肤感染部位获取的血液样本进行的。在这种情况下，当前的项目旨在表征控制血液和皮肤中利什曼尼亚涉及的免疫机制。在此提案中，我们旨在在人类局部皮肤（LCL）和粘膜皮肤利什曼病（MCL）的研究中首次应用这种既定方法，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力的详细成分，并确定这些因素中的哪一个可以推动病变的发育或/和寄生虫控制。结果还将提供重要的数据，以增加对利什曼原虫免疫力的理解，从而提供有关皮肤和胶质可素利什曼病患者中观察到的病理差异的解释，并有助于改善未来疫苗和药物靶标的设计。

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.

• 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