Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia.
PLoS Negl Trop Dis. 2012;6(6):e1684. doi: 10.1371/journal.pntd.0001684. Epub 2012 Jun 12.
Cutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood.
METHODOLOGY/PRINCIPAL FINDINGS: We have recently shown in an experimental model of cutaneous leishmaniasis that arginase-induced L-arginine metabolism suppresses antigen-specific T cell responses at the site of pathology, but not in the periphery. To test whether these results translate to human disease, we recruited patients presenting with localized lesions of cutaneous leishmaniasis and assessed the levels of arginase activity in cells isolated from peripheral blood and from skin biopsies. Arginase activity was similar in peripheral blood mononuclear cells (PBMCs) from patients and healthy controls. In sharp contrast, arginase activity was significantly increased in lesion biopsies of patients with localized cutaneous leishmaniasis as compared with controls. Furthermore, we found that the expression levels of CD3ζ, CD4 and CD8 molecules were considerably lower at the site of pathology as compared to those observed in paired PBMCs.
Our results suggest that increased arginase in lesions of patients with cutaneous leishmaniasis might play a role in the pathogenesis of the disease by impairing T cell effector functions.
皮肤利什曼病是一种由寄生虫利什曼原虫引起的经媒介传播的疾病，在埃塞俄比亚主要由寄生虫利什曼原虫引起。这种被忽视的热带病在农村地区很常见，会导致严重的发病率。持续性不愈合的皮肤利什曼病与 T 细胞介导的反应不佳有关；然而，其潜在机制尚不清楚。
方法/主要发现：我们最近在皮肤利什曼病的实验模型中表明，诱导型一氧化氮合酶诱导的 L-精氨酸代谢会抑制病理部位的抗原特异性 T 细胞反应，但不会在周围发生。为了测试这些结果是否适用于人类疾病，我们招募了患有局部皮肤利什曼病的患者，并评估了从外周血和皮肤活检中分离的细胞中精氨酸酶活性的水平。患者和健康对照组的外周血单核细胞（PBMC）中的精氨酸酶活性相似。相比之下，患有局限性皮肤利什曼病的患者病变活检中的精氨酸酶活性明显升高。此外，我们发现与配对 PBMC 相比，在病理部位 CD3ζ、CD4 和 CD8 分子的表达水平明显降低。
我们的结果表明，皮肤利什曼病患者病变中的精氨酸酶增加可能通过损害 T 细胞效应功能在疾病发病机制中起作用。
