Kumar Rajiv, Chauhan Shashi Bhushan, Ng Susanna S, Sundar Shyam, Engwerda Christian R
Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, India.
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Front Immunol. 2017 Nov 8;8:1492. doi: 10.3389/fimmu.2017.01492. eCollection 2017.
Leishmaniasis encompasses a group of diseases caused by protozoan parasites belonging to the genus . These diseases range from life threatening visceral forms to self-healing cutaneous lesions, and each disease manifestations can progress to complications involving dissemination of parasites to skin or mucosal tissue. A feature of leishmaniasis is the key role host immune responses play in disease outcome. T cells are critical for controlling parasite growth. However, they can also contribute to disease onset and progression. For example, potent regulatory T cell responses can develop that suppress antiparasitic immunity. Alternatively, hyperactivated CD4 or CD8 T cells can be generated that cause damage to host tissues. There is no licensed human vaccine and drug treatment options are often limited and problematic. Hence, there is an urgent need for new strategies to improve the efficacy of current vaccine candidates and/or enhance both antiparasitic drug effectiveness and subsequent immunity in treated individuals. Here, we describe our current understanding about host immune responses contributing to disease protection and progression in the various forms of leishmaniasis. We also discuss how this knowledge may be used to develop new strategies for host-directed immune therapy to prevent or treat leishmaniasis. Given the major advances made in immune therapy in the cancer and autoimmune fields in recent years, there are significant opportunities to ride on the back of these successes in the infectious disease domain. Conversely, the rapid progress in our understanding about host immune responses during leishmaniasis is also providing opportunities to develop novel immunotherapy strategies that could have broad applications in diseases characterized by inflammation or immune dysfunction.
利什曼病是由利什曼原虫属的原生动物寄生虫引起的一组疾病。这些疾病范围从危及生命的内脏型到可自愈的皮肤病变，每种疾病表现都可能进展为并发症，包括寄生虫扩散至皮肤或粘膜组织。利什曼病的一个特点是宿主免疫反应在疾病转归中起关键作用。T细胞对于控制寄生虫生长至关重要。然而，它们也可能导致疾病的发生和进展。例如，可能会产生强大的调节性T细胞反应，抑制抗寄生虫免疫。或者，可能会产生过度活化的CD4或CD8 T细胞，对宿主组织造成损害。目前尚无获批的人类疫苗，药物治疗选择往往有限且存在问题。因此，迫切需要新策略来提高当前候选疫苗的效力和/或增强抗寄生虫药物的疗效以及治疗个体随后的免疫力。在此，我们描述了目前对宿主免疫反应在各种形式利什曼病的疾病保护和进展中所起作用的理解。我们还讨论了如何利用这些知识来开发针对宿主的免疫治疗新策略，以预防或治疗利什曼病。鉴于近年来癌症和自身免疫领域免疫治疗取得的重大进展，在传染病领域借助这些成功经验有很大机会。相反，我们对利什曼病期间宿主免疫反应的理解迅速进展，也为开发可能在以炎症或免疫功能障碍为特征的疾病中广泛应用的新型免疫治疗策略提供了机会。
