Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil; Instituto de Pesquisa Clínica Carlos Borborema, Fundação de Medicina Tropical Dr, Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil; Laboratório de Genômica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, AM, Brazil; Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil..
Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil; Instituto de Pesquisa Clínica Carlos Borborema, Fundação de Medicina Tropical Dr, Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil; Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil.; Universidade Nilton Lins (UNINILTONLINS), Manaus, AM, Brazil.
Cytokine. 2018 Oct;110:374-380. doi: 10.1016/j.cyto.2018.04.008. Epub 2018 Apr 12.
The efficiency of the immune system has been shaped throughout the evolutionary process allowing adaptations. In a Plasmodium vivax infection, the host attempts to develop an innate immune response to keep in check the parasite that is associated with inflammatory and regulatory processes. Production of pro-inflammatory and regulatory cytokines simultaneously appears to be a balancing mechanism for the host to prevent the onset of severe disease. Changes in the dynamics of circulating cytokines production can influence the pathogenesis, severity of the disease and episodes of recurrent Plasmodium vivax malaria (Pv-malaria). A cross-sectional study was conducted in endemic areas for Pv-malaria in the Amazonas State, Brazil. Several SNPs in TLR genes were genotyped by PCR-RFLP in 137 patients infected with P. vivax. Circulating cytokines IL-6, TNF, IL-2, IL-10, IFN-γ and IL-4 were measured by CBA. Influence of the studied SNPs on circulating cytokines was investigated by applying the Kruskal-Wallis test followed by Dunns' multiple comparison post-test. A Spearman correlation test also was performed to elaborate circulating cytokine networks and to demonstrate the level of interaction between each molecule. Individuals with genotypes A/G (TLR4 A299G), C/C (TLR6 S249P) and T/T (TLR9 -1486C/T) appear to produce less/gain IL-6, IFN-γ, IL-10, IL-2 and IL-4 compared to patients with wild-type and heterozygous genotypes. In addition, these genotypes seem to influence the interaction network between the molecules studied, causing a lower interaction, absence or even negative interaction between the cytokines. Data presented in this study suggests the influence of polymorphisms TLR4 (A299G), TLR6 (S249P) and TLR9 (-1486C/T) on the production of circulating cytokines during Pv-malaria.
免疫系统的效率在进化过程中得到了塑造，从而允许了适应性的产生。在间日疟原虫感染中，宿主试图发展先天免疫反应来控制寄生虫，这与炎症和调节过程有关。促炎和调节细胞因子的同时产生似乎是宿主的一种平衡机制，以防止严重疾病的发生。循环细胞因子产生的动力学变化会影响发病机制、疾病的严重程度和间日疟原虫复发疟疾（Pv-疟疾）的发作。在巴西亚马逊州间日疟原虫流行地区进行了一项横断面研究。在 137 名感染间日疟原虫的患者中，通过 PCR-RFLP 对 TLR 基因的多个 SNPs 进行了基因分型。通过 CBA 测量了循环细胞因子 IL-6、TNF、IL-2、IL-10、IFN-γ 和 IL-4。通过应用 Kruskal-Wallis 检验 followed by Dunns' multiple comparison post-test 研究了所研究的 SNPs 对循环细胞因子的影响。还进行了 Spearman 相关性检验，以阐述循环细胞因子网络，并展示每个分子之间的相互作用水平。与野生型和杂合基因型的患者相比，TLR4 A299G 基因型的个体（A/G）、TLR6 S249P 基因型的个体（C/C）和 TLR9 -1486C/T 基因型的个体似乎产生较少的/获得 IL-6、IFN-γ、IL-10、IL-2 和 IL-4。此外，这些基因型似乎影响了所研究分子之间的相互作用网络，导致细胞因子之间的相互作用降低、缺失甚至负相互作用。本研究的数据表明 TLR4（A299G）、TLR6（S249P）和 TLR9（-1486C/T）多态性对间日疟原虫感染期间循环细胞因子产生的影响。
