Shete Ashwini, Bichare Shubhangi, Pujari Vishwanath, Virkar Rashmi, Thakar Madhuri, Ghate Manisha, Patil Sandip, Vyakarnam Annapurna, Gangakhedkar Raman, Bai Gaowa, Niki Toshiro, Hattori Toshio
ICMR-National AIDS Research Institute, Pune, India.
B. J. Medical College and Sassoon General Hospital, Pune, India.
Front Microbiol. 2020 Jul 17;11:1685. doi: 10.3389/fmicb.2020.01685. eCollection 2020.
Galectin-9 (Gal-9) and osteopontin (OPN) play immunomodulatory roles in tuberculosis and HIV infections. Evaluation of their levels as well as their interplay with different pro-inflammatory cytokines is critical to understand their role in immunopathogenesis of HIV/tuberculosis co-infection considering the complexity of the disease. Plasma levels of these proteins were measured by ELISAs in HIV-negative individuals with pulmonary ( = 21), extrapulmonary ( = 33), and latent tuberculosis ( = 22) and in HIV infected patients with pulmonary ( = 14), latent tuberculosis ( = 17), and without tuberculosis ( = 41). Levels of pro-inflammatory cytokines were estimated by Luminex assay. Receiver operated characteristic curve analysis was performed to evaluate discriminatory roles of these proteins. Spearman's correlation analysis was performed with the markers of HIV and tuberculosis disease progression to evaluate their immunopathogenic roles. Gal-9 and OPN levels were higher in HIV uninfected patients with active tuberculosis than with latent tuberculosis. Gal-9 but not OPN levels were higher in HIV infected patients with active tuberculosis than with latent tuberculosis. Area under curve for Galectin-9 was >0.9 in HIV/tuberculosis co-infection and extrapulmonary tuberculosis. OPN and IL-6 levels were higher in patients with severe chest X-ray grade indicating its association with severity of the disease and positively correlated with each other. Stronger positive and negative correlations of Gal-9 levels, respectively, with viral loads and CD4 cell counts in HIV infected patients were observed than OPN levels indicating their association with HIV disease progression. Thus, significantly elevated Gal-9 levels were reported for the first time in HIV/tuberculosis co-infection and extrapulmonary tuberculosis in our study than single infections with HIV and tuberculosis. The study indicated a need for further evaluation of monitoring role of Gal-9 for detection of developing tuberculosis in HIV infected individuals. The findings also indicated differential roles of Gal-9 and OPN in the pathogenesis of tuberculosis and HIV infections.
半乳糖凝集素-9（Gal-9）和骨桥蛋白（OPN）在结核病和HIV感染中发挥免疫调节作用。鉴于该疾病的复杂性，评估它们的水平以及它们与不同促炎细胞因子的相互作用对于理解它们在HIV/结核病合并感染免疫发病机制中的作用至关重要。通过酶联免疫吸附测定法（ELISA）测量了患有肺结核（n = 21）、肺外结核（n = 33）和潜伏性结核（n = 22）的HIV阴性个体以及患有肺结核（n = 14）、潜伏性结核（n = 17）和无结核病（n = 41）的HIV感染患者血浆中这些蛋白质的水平。通过Luminex检测法估算促炎细胞因子的水平。进行受试者操作特征曲线分析以评估这些蛋白质的鉴别作用。采用Spearman相关性分析HIV和结核病疾病进展标志物，以评估它们的免疫致病作用。与潜伏性结核相比，患有活动性结核的未感染HIV患者中Gal-9和OPN水平更高。与潜伏性结核相比，患有活动性结核的HIV感染患者中Gal-9水平更高，但OPN水平并非如此。在HIV/结核病合并感染和肺外结核中，半乳糖凝集素-9的曲线下面积>0.9。胸部X线分级严重的患者中OPN和IL-6水平更高，表明其与疾病严重程度相关且两者呈正相关。与OPN水平相比，观察到HIV感染患者中Gal-9水平分别与病毒载量和CD4细胞计数呈更强的正相关和负相关，表明它们与HIV疾病进展相关。因此，在我们的研究中，首次报道HIV/结核病合并感染和肺外结核中Gal-9水平显著高于HIV和结核病单一感染。该研究表明需要进一步评估Gal-9在检测HIV感染个体中结核病进展的监测作用。研究结果还表明Gal-9和OPN在结核病和HIV感染发病机制中的作用存在差异。
