Kumar Nathella Pavan, Banurekha Vaithilingam V, Nair Dina, Babu Subash
National Institutes of Health-NIRT- International Center for Excellence in Research, Chennai, India.
National Institutes for Research in Tuberculosis, Chennai, India.
PLoS One. 2017 Apr 27;12(4):e0176495. doi: 10.1371/journal.pone.0176495. eCollection 2017.
The immune response to tuberculosis (TB) is T cell dependent. T cells are the major facilitators of protection and effector functions with CD4+ T cells being the most important players, followed by CD8+ T cells. The common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 play a vital role in peripheral T cell growth and survival. However, the role of common γ-chain cytokines in pulmonary TB (PTB) is poorly understood.
To examine the association of circulating common γ-chain cytokines with TB disease or infection, we examined the systemic levels of IL-2, IL-7, IL-15, and IL-21 in individuals with PTB, latent TB (LTB) or no TB infection (NTB). We also examined the levels of these cytokines in PTB individuals before and after anti-tuberculosis treatment.
Circulating levels of IL-2, IL-7 and IL-21 were significantly diminished in PTB compared to LTB or NTB individuals. Moreover, TB antigen stimulated whole blood also exhibited diminished levels of common γ-chain cytokines in PTB compared to LTB or NTB individuals. The plasma levels of common γ-chain cytokines exhibited no significant association with the severity or extent of TB disease or with bacterial burdens. However, upon standard anti-TB treatment, both the systemic as well as the TB antigen stimulated levels of IL-2, IL-7 and IL-21 were significantly increased in PTB individuals.
Therefore our data demonstrate that diminished levels of common γ-chain cytokines are a common characteristic of PTB and potentially highlight the importance of boosting these responses to improve treatment outcomes.
对结核病(TB)的免疫反应依赖于T细胞。T细胞是保护和效应功能的主要促进者,其中CD4+ T细胞是最重要的参与者,其次是CD8+ T细胞。常见的γ链细胞因子白细胞介素-2(IL-2)、白细胞介素-7(IL-7)、白细胞介素-15(IL-15)和白细胞介素-21(IL-21)在外周T细胞生长和存活中起着至关重要的作用。然而,常见γ链细胞因子在肺结核(PTB)中的作用尚不清楚。
为了研究循环中常见γ链细胞因子与结核病或感染的关联,我们检测了肺结核患者、潜伏性结核(LTB)患者或无结核感染(NTB)个体中IL-2、IL-7、IL-15和IL-21的全身水平。我们还检测了抗结核治疗前后肺结核患者中这些细胞因子的水平。
与LTB或NTB个体相比,PTB患者中IL-2、IL-7和IL-21的循环水平显著降低。此外,与LTB或NTB个体相比,结核抗原刺激的全血中PTB患者常见γ链细胞因子水平也降低。常见γ链细胞因子的血浆水平与结核病的严重程度或范围以及细菌载量均无显著关联。然而,在标准抗结核治疗后,PTB患者中IL-2、IL-7和IL-21的全身水平以及结核抗原刺激水平均显著升高。
因此,我们的数据表明,常见γ链细胞因子水平降低是PTB的一个共同特征,并可能突出增强这些反应以改善治疗效果的重要性。