Alves Mota Camila, Stéfanie Sara Lopes Lera-Nonose Daniele, Ávila Brustolin Aline, Chiqueto Duarte Giovanna, Carolina Mota Dos Santos Maria, Valdrinez Campana Lonardoni Maria, Gomes Verzignassi Silveira Thaís
Programa de Pós-Graduação em Ciências da Saúde, Universidade Estadual de Maringá, Maringá, Paraná, Brasil.
Programa de Pós-Graduação em Ciências da Saúde, Universidade Estadual de Maringá, Maringá, Paraná, Brasil.
Cytokine. 2022 May;153:155833. doi: 10.1016/j.cyto.2022.155833. Epub 2022 Mar 2.
Leishmania (Viannia) species are the major agents of cutaneous leishmaniasis (CL) in the Americas. Ulcerative stigmatizing skin lesions generally characterize CL. The microenvironment during Leishmania infection is rich in inflammatory cells and molecules, which contrasts with low oxygen levels. The hypoxia-inducible factor (HIF)-1α activates several genes in response to hypoxia and inflammatory reactions, but its role in the CL course is poorly understood. We investigated the expression pattern of the genes HIF-1α, arginase, inducible NO synthase (iNOS), interferon (IFN)-γ, interleukin (IL)-12, and IL-10 in skin lesions and lymph nodes of golden hamsters infected with L. braziliensis, L. lainsoni, and L. naiffi. The animals were infected and followed for 105 days, with paw volume measurements and photos taken weekly. Euthanasia was performed at 0, 15, 56, and 105 days post-infection. The parasite load of paw and lymph node tissues were measured through absolute quantification at real-time PCR (qPCR), and reverse transcription qPCR (RT-qPCR) was applied to demonstrate the relative mRNA expression of the target genes. Among groups, animals infected with L. braziliensis had the highest parasite load in paws and lymph nodes. HIF-1α mRNA was down-regulated during chronic Leishmania (Viannia) infection but demonstrated less inhibition in hamsters infected with L. lainsoni and L. naiffi. Arginase was the most detectable gene in animals infected by L. braziliensis; IFN-γ and IL-10 genes were the most detectable in L. lainsoni and L. naiffi-infected animals. HIF-1α gene transcription seemed to be down-modulated byL. (Viannia)infection and was less inhibited by L. lainsoni and L. naiffi when compared toL. braziliensis. Animals with L. lainsoni and L. naiffi showed better control of the disease. Further studies are necessary to evaluate the mechanism influencing HIF-1α expression and its role on CL protection; such research could elucidate potential use of HIF-1α as a therapeutic target.
利什曼原虫（维阿尼亚种）是美洲皮肤利什曼病（CL）的主要病原体。溃疡性有瘢痕的皮肤病变是CL的一般特征。利什曼原虫感染期间的微环境富含炎症细胞和分子，这与低氧水平形成对比。缺氧诱导因子（HIF）-1α会响应缺氧和炎症反应激活多个基因，但其在CL病程中的作用尚不清楚。我们研究了感染巴西利什曼原虫、赖氏利什曼原虫和奈菲利什曼原虫的金黄仓鼠皮肤病变和淋巴结中HIF-1α、精氨酸酶、诱导型一氧化氮合酶（iNOS）、干扰素（IFN）-γ、白细胞介素（IL）-12和IL-10基因的表达模式。动物被感染并随访105天，每周测量爪体积并拍照。在感染后0、15、56和105天实施安乐死。通过实时PCR（qPCR）的绝对定量测量爪和淋巴结组织的寄生虫载量，并应用逆转录qPCR（RT-qPCR）来证明靶基因的相对mRNA表达。在各实验组中，感染巴西利什曼原虫的动物爪和淋巴结中的寄生虫载量最高。HIF-1α mRNA在慢性利什曼原虫（维阿尼亚种）感染期间下调，但在感染赖氏利什曼原虫和奈菲利什曼原虫的仓鼠中受到的抑制较小。精氨酸酶是感染巴西利什曼原虫的动物中最易检测到的基因；IFN-γ和IL-10基因在感染赖氏利什曼原虫和奈菲利什曼原虫的动物中最易检测到。HIF-1α基因转录似乎受到利什曼原虫（维阿尼亚种）感染的下调，与巴西利什曼原虫相比，赖氏利什曼原虫和奈菲利什曼原虫对其抑制作用较小。感染赖氏利什曼原虫和奈菲利什曼原虫的动物对疾病的控制更好。有必要进行进一步研究以评估影响HIF-1α表达的机制及其在CL保护中的作用；此类研究可能阐明将HIF-1α用作治疗靶点的潜在用途。
