Gomes Clayson M, Ávila Lucilla R, Santos Jéssica C, Oliveira Pollyana G, Tomé Fernanda D, Pereira Ledice I A, Dorta Miriam L, Lino Ruy S, Ribeiro-Dias Fátima, Oliveira Milton A P
Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil Medical and Pharmaceutical Sciences School, Pontifical Catholic University of Goiás, Goiânia, GO 74605010, Brazil.
Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
Pathog Dis. 2016 Jun;74(4):ftw023. doi: 10.1093/femspd/ftw023. Epub 2016 Apr 11.
Mucosal leishmaniasis (ML) caused by Leishmania (Vianna) braziliensis usually appears after the healing of the primary lesion when amastigotes disseminate from the infection site to the mucosal area. Here, we investigated murine infection with amastigotes obtained from patients with ML or localized cutaneous leishmaniasis (LCL). Amastigotes were used to infect wild type, IFN-γ KO and inducible nitric oxide synthase (iNOS) KO mice. Amastigotes from patients with LCL induced lesions that appeared earlier in IFN-γ KO than parasites from ML. The lesion after infection with ML appeared early in iNOS KO than in IFN-γ KO mice and in iNOS KO mice parasites from ML and LCL cause similar lesions at the initial phase of infection, while parasites from ML induced greater lesions than the ones from LCL at the late phase. A greater number of parasites were observed in spleen of IFN-γ KO and iNOS KO mice infected with amastigotes from patients with ML than those with LCL. Parasites from ML infect a lower percentage of macrophages and are killed independent on IFN-γ and dependent on NO. The data suggest that amastigotes responsible for mucosal lesion in humans develop slowly on the initial phase of infection due to high susceptibility to NO and they have an increased ability to disseminate.
由巴西利什曼原虫（维安亚利什曼原虫）引起的黏膜利什曼病（ML）通常在原发性病变愈合后出现，此时无鞭毛体从感染部位扩散到黏膜区域。在此，我们研究了用从ML患者或局限性皮肤利什曼病（LCL）患者获得的无鞭毛体感染小鼠的情况。无鞭毛体被用于感染野生型、IFN-γ基因敲除小鼠和诱导型一氧化氮合酶（iNOS）基因敲除小鼠。来自LCL患者的无鞭毛体诱导的病变在IFN-γ基因敲除小鼠中比来自ML的寄生虫出现得更早。与IFN-γ基因敲除小鼠相比，ML感染后iNOS基因敲除小鼠的病变出现得更早，并且在iNOS基因敲除小鼠中，来自ML和LCL的寄生虫在感染初期引起的病变相似，而在后期，来自ML的寄生虫比来自LCL的寄生虫诱导的病变更大。在感染来自ML患者无鞭毛体的IFN-γ基因敲除小鼠和iNOS基因敲除小鼠的脾脏中观察到的寄生虫数量比感染来自LCL患者无鞭毛体的小鼠更多。来自ML的寄生虫感染巨噬细胞的比例较低，并且其被杀死不依赖于IFN-γ，而是依赖于NO。数据表明，导致人类黏膜病变的无鞭毛体在感染初期由于对NO高度敏感而发育缓慢，并且它们具有更强的扩散能力。
