Department of Microbiology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Av. Prof. Moraes Rego S/N, 50670-420 Recife, Pernambuco, Brazil; Central Laboratory of Public Health Dr Milton Bezerra de Sobral, Rua João Fernandes Vieira S/N, 50050-215 Recife, Pernambuco, Brazil.
Department of Microbiology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Av. Prof. Moraes Rego S/N, 50670-420 Recife, Pernambuco, Brazil.
Cytokine. 2019 Nov;123:154784. doi: 10.1016/j.cyto.2019.154784. Epub 2019 Jul 23.
Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is the most spread clinical form of leishmaniasis in Brazil. However, only a few part of the people infected develop clinically perceptive disease, suggesting the influence of human genetic components in the CL pathogeny. The rs2275913 SNP is the nucleotide variant of the IL17A gene. The A allele is associated with a vast number of infectious and non-infectious diseases. Here, we investigated the association of the rs2275913 SNP (G/A) from IL-17A and two forms of susceptibility to CL in Brazil by case-control study. Furthermore, we evaluated the functional relevance of this SNP during the immune response of the host and analyzed its impact in the parasite elimination. Weak associations of A allele with susceptibility to L. braziliensis infection or to symptomatic CL were observed, and a tendency of A allele carriers to be more susceptible to infection and cutaneous disease. Functional analysis of the Th17 cell phenotypes revealed lower frequencies of CD4+ IL-17+ cells in samples of infected people with AA/AG genotypes. Furthermore, people carrying the A allele maintain higher parasite loads, reinforcing the genetic susceptibility findings. This study adds knowledge about the influence of a significant genetic variation on IL-17 promoter on CL pathogenesis, and may contribute to enhance the knowledge about the role of IL-17 in the L. braziliensis infections.
巴西利什曼原虫引起的皮肤利什曼病（CL）是巴西最常见的临床利什曼病形式。然而，只有少数感染的人会出现临床明显的疾病，这表明人类遗传成分在 CL 发病机制中起作用。rs2275913 SNP 是 IL17A 基因的核苷酸变异。A 等位基因与大量的感染性和非感染性疾病有关。在这里，我们通过病例对照研究调查了巴西 CL 两种易感性形式与 IL-17A 基因 rs2275913 SNP（G/A）的关联。此外，我们评估了该 SNP 在宿主免疫反应中的功能相关性，并分析了其对寄生虫清除的影响。A 等位基因与 L. braziliensis 感染易感性或症状性 CL 易感性的弱关联，以及 A 等位基因携带者更易感染和发生皮肤疾病的趋势。Th17 细胞表型的功能分析显示，AA/AG 基因型感染者样本中 CD4+IL-17+细胞的频率较低。此外，携带 A 等位基因的人保持更高的寄生虫载量，这进一步证实了遗传易感性的发现。这项研究增加了关于 IL-17 启动子的重要遗传变异对 CL 发病机制影响的知识，可能有助于增强对 IL-17 在巴西利什曼原虫感染中的作用的了解。
