Laboratory of Immunophysiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Immunopharmacology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Front Cell Infect Microbiol. 2023 Jun 12;13:1192800. doi: 10.3389/fcimb.2023.1192800. eCollection 2023.
Leishmaniasis is a neglected tropical parasitic disease with few approved medications. Cutaneous leishmaniasis (CL) is the most frequent form, responsible for 0.7 - 1.0 million new cases annually worldwide. Leukotrienes are lipid mediators of inflammation produced in response to cell damage or infection. They are subdivided into leukotriene B4 (LTB) and cysteinyl leukotrienes LTC4 and LTD4 (Cys-LTs), depending on the enzyme responsible for their production. Recently, we showed that LTB could be a target for purinergic signaling controlling infection; however, the importance of Cys-LTs in the resolution of infection remained unknown. Mice infected with are a model of CL infection and drug screening. We found that Cys-LTs control infection in susceptible (BALB/c) and resistant (C57BL/6) mouse strains. , Cys-LTs significantly diminished the infection index in peritoneal macrophages of BALB/c and C57BL/6 mice. , intralesional treatment with Cys-LTs reduced the lesion size and parasite loads in the infected footpads of C57BL/6 mice. The anti-leishmanial role of Cys-LTs depended on the purinergic P2X7 receptor, as infected cells lacking the receptor did not produce Cys-LTs in response to ATP. These findings suggest the therapeutic potential of LTB4 and Cys-LTs for CL treatment.
利什曼病是一种被忽视的热带寄生虫病，批准的药物很少。皮肤利什曼病（CL）是最常见的形式，每年在全球范围内导致 0.7-100 万例新发病例。白三烯是对细胞损伤或感染产生的炎症脂质介质。根据负责其产生的酶，它们分为白三烯 B4（LTB）和半胱氨酰白三烯 LTC4 和 LTD4（Cys-LTs）。最近，我们表明 LTB 可能是嘌呤能信号控制感染的靶点；然而，Cys-LTs 在感染的解决中的重要性仍然未知。感染的小鼠是 CL 感染和药物筛选的模型。我们发现 Cys-LTs 控制易感（BALB/c）和抗性（C57BL/6）小鼠菌株中的感染。此外，Cys-LTs 显著降低了 BALB/c 和 C57BL/6 小鼠腹腔巨噬细胞中的感染指数。此外，局部给予 Cys-LTs 可减少 C57BL/6 小鼠感染足垫的病变大小和寄生虫负荷。Cys-LTs 的抗利什曼作用取决于嘌呤能 P2X7 受体，因为缺乏该受体的感染细胞不会对 ATP 产生 Cys-LTs。这些发现表明 LTB4 和 Cys-LTs 具有治疗 CL 的潜力。
