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Abstract：
Leishmania are protozoan parasites that predominantly reside in myeloid cells within their mammalian hosts. Monocytes and macrophages play a central role in the pathogenesis of all forms of leishmaniasis, including cutaneous and visceral leishmaniasis. The present review will highlight the diverse roles of macrophages in leishmaniasis as initial replicative niche, antimicrobial effectors, immunoregulators and as safe hideaway for parasites persisting after clinical cure. These multiplex activities are either ascribed to defined subpopulations of macrophages (e.g., Ly6ChighCCR2+ inflammatory monocytes/monocyte-derived dendritic cells) or result from different activation statuses of tissue macrophages (e.g., macrophages carrying markers of of classical [M1] or alternative activation [M2]). The latter are shaped by immune- and stromal cell-derived cytokines (e.g., IFN-γ, IL-4, IL-10, TGF-β), micro milieu factors (e.g., hypoxia, tonicity, amino acid availability), host cell-derived enzymes, secretory products and metabolites (e.g., heme oxygenase-1, arginase 1, indoleamine 2,3-dioxygenase, NOS2/NO, NOX2/ROS, lipids) as well as by parasite products (e.g., leishmanolysin/gp63, lipophosphoglycan). Exciting avenues of current research address the transcriptional, epigenetic and translational reprogramming of macrophages in a Leishmania species- and tissue context-dependent manner.
摘要：
利什曼原虫是主要存在于其哺乳动物宿主内的骨髓细胞中的原生动物寄生虫。单核细胞和巨噬细胞在所有形式的利什曼病的发病机理中起着核心作用，包括皮肤和内脏利什曼病。本综述将强调巨噬细胞在利什曼病中作为初始复制生态位的不同作用。抗菌效应，免疫调节剂，并作为临床治愈后持续存在的寄生虫的安全藏身之处。这些多重活性要么归因于确定的巨噬细胞亚群(例如，Ly6ChighCCR2+炎性单核细胞/单核细胞衍生的树突状细胞)或来自组织巨噬细胞的不同激活状态(例如，携带经典[M1]或替代激活[M2]标记的巨噬细胞)。后者由免疫和基质细胞衍生的细胞因子形成(例如，IFN-γ，IL-4，IL-10，TGF-β），微观环境因素(例如，缺氧,张力,氨基酸可用性)，宿主细胞衍生的酶，分泌产物和代谢物(例如，血红素加氧酶-1，精氨酸酶1，吲哚胺2,3-双加氧酶，NOS2/NO,NOX2/ROS,脂质)以及寄生虫产物(例如，leishmanolysin/gp63，脂磷酰聚糖）。当前研究的令人兴奋的途径解决了转录，利什曼原虫物种和组织环境依赖性方式中巨噬细胞的表观遗传和翻译重编程。
