Plasma levels of Galectin-9 reflect disease severity in malaria infection.
Plasma levels of Galectin-9 reflect disease severity in malaria infection.
复制标题
乳糖素9的血浆水平反映疟疾感染中的疾病严重程度。
DOI：
10.1186/s12936-016-1471-7
复制
发表时间：
2016-08-11
期刊：
影响因子：
3
通讯作者：
Hattori T
中科院分区：
文献类型：
--
作者：
Dembele BP;Chagan-Yasutan H;Niki T;Ashino Y;Tangpukdee N;Shinichi E;Krudsood S;Kano S;Hattori T
半乳糖凝集素-9 （Gal-9）是一种β-半乳糖苷结合凝集素，与细胞和病原体的糖蛋白和糖脂上的糖部分相互作用。Gal-9被认为是一种免疫调节剂，通过与T细胞免疫球蛋白和粘蛋白结构域3 （Tim3）相互作用诱导细胞死亡，Tim3是一种共抑制受体，它抑制几种促炎细胞因子（TNF、IL-6和IL-1α）的产生，并增强IL-10的产生。为了了解疟疾的免疫病理，我们测量了血浆中的Gal-9。在第0天、第7天和第28天三个时间点采集了泰国50例急性疟疾病例（9例重症病例和41例无并发症病例）的血浆样本和临床参数。ELISA法检测血清Gal-9水平。总共38种细胞因子和趋化因子被测量使用BioPlex试验。与第7天和第28天相比，第0天Gal-9水平较高（P < 0.0001）。在第0天和第7天，严重疟疾（SM）病例的Gal-9水平也高于无并发症（UM）病例（分别为923 vs 617 pg/mL， P = 0.03和659 vs 348 pg/mL， P = 0.02）。第0天血尿素氮/肌酐比值（BUN/肌酐）≥20 （mg/dL）的患者中位Gal-9水平高于BUN/肌酐<20 （mg/dL）的患者（817.3 vs 576.2 pg/mL, P = 0.007）。在SM和UM病例中，Gal-9与氯化物水平呈显著负相关（rs = - 0.73和rs = - 0.46）。在UM和SM病例中，Gal-9与促炎性和抗炎性细胞因子和趋化因子如TNF、IL-6、IFN-α2、IFN-γ、IL-1Ra和IL-10显著相关。这些相关性在第0天观察到，但在第28天消失。Gal-9在急性疟疾期间释放，反映了其严重程度。急性疟疾感染中Gal-9的升高提高了其通过与Gal-9受体Tim-3结合而终止免疫反应的可能性。
Galectin-9 (Gal-9) is a β-galactoside-binding lectin that interacts with sugar moieties on glycoproteins and glycolipids of cells and pathogens. Gal-9 is known as an immune modulator that induces cell death via interaction with T cell immunoglobulin and mucin domain-3 (Tim3), a co-inhibitory receptor, and it inhibits production of several pro-inflammatory cytokines (TNF, IL-6 and IL-1α) and enhances production of IL-10. To understand the immune pathology of malaria, the Gal-9 in plasma was measured. Plasma samples and clinical parameters were obtained from 50 acute malaria cases (nine severe and 41 uncomplicated cases) from Thailand at three time points: day 0, day 7 and day 28. Gal-9 levels were determined by ELISA. A total of 38 species of cytokines and chemokines were measured using a BioPlex assay. Gal-9 levels were higher at day 0 compared to day 7 and day 28 (P < 0.0001). Gal-9 levels were also higher in severe malaria (SM) cases compared to uncomplicated (UM) cases at day 0 and day 7 (923 vs 617 pg/mL; P = 0.03, and 659 vs 348 pg/mL; P = 0.02 respectively). Median Gal-9 levels were higher in patients with blood urea nitrogen to creatinine ratio (BUN/creatinine) ≥20 (mg/dL) than in patients with BUN/creatinine <20 (mg/dL) at day 0 (817.3 vs 576.2 pg/mL, P = 0.007). Gal-9 was inversely significantly correlated with chloride levels in both SM and UM cases (rs = −0.73 and rs = −0.46, respectively). In both UM and SM cases, Gal-9 was significantly associated with pro- and anti-inflammatory cytokines and chemokines such as TNF, IL-6, IFN-α2, IFN-γ, IL-1Ra and IL-10. These correlations were observed at day 0 but disappeared at day 28. Gal-9 is released during acute malaria, and reflects its severity. This elevation of Gal-9 in acute malaria infection raises the possibility of its role in termination of the immune response by binding to Tim-3, a receptor of Gal-9.