Laboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, GO, Brazil.
Front Immunol. 2024 Feb 22;15:1343602. doi: 10.3389/fimmu.2024.1343602. eCollection 2024.
Single nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production.
We genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants.
In participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis.
单核苷酸变异（SNV）是一种常见于人群中的特定遗传变异，通常不会表现出表型。然而，根据其位置和交换的核苷酸类型，SNV 可以改变或抑制其所在基因的功能。免疫球蛋白 G（IgG）受体基因表现出多种多态性，包括 rs1801274，它存在于 FcgRIIa 基因中。A 被 T 取代导致组氨酸（H）被精氨酸（R）取代，从而改变 IgG 受体对 IgG 亚型和 C 反应蛋白（CRP）的亲和力。在这项研究中，我们分析了 rs1801274 及其与 L. infantum 摄取和细胞因子产生的功能相关性。
我们对来自内脏利什曼病流行地区的 201 名个体进行基因分型，使用 Taqman 探针对候选基因进行 rs1801274 检测。此外，我们还包括了来自非流行地区的 70 名个体进行功能研究。随后，我们分离并培养了来自非流行地区的参与者外周血中的一周贴壁单核细胞（AMCs），在存在 L. infantum 前鞭毛体的情况下，有无抗原特异性 IgG 和/或 CRP。我们分析了吞噬率和培养上清液中一氧化氮（NO）、肿瘤坏死因子（TNF）-a、白细胞介素（IL）-10、IL-12 p70、IL-1b、IL-6 和 IL-8 的产生。
在来自流行地区的参与者中，A/G（H/R 同种型）杂合基因型与疾病易感性显著相关。此外，SNV 以依赖调理的方式诱导吞噬率的变化。用 IgG 调理增加了具有 H/R 同种型的 AMCs 中 IL-10、TNF-a 和 IL-6 的产生，随后降低了 NO 的产生。这里提出的结果表明，rs1801274 多态性与内脏利什曼病的易感性增加有关。
