Anuradha Rajamanickam, Munisankar Saravanan, Bhootra Yukthi, Dolla Chandrakumar, Kumaran Paul, Nutman Thomas B, Babu Subash
National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
National Institute for Research in Tuberculosis, Chennai, India.
Infect Immun. 2017 Mar 23;85(4). doi: 10.1128/IAI.00973-16. Print 2017 Apr.
Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with LTB and with or without coexistent infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent infection have significantly lower levels of systemic and TB antigen-stimulated type 1 (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated type 2 (IL-4 and IL-5) and regulatory (transforming growth factor beta [TGF-β]) cytokines. Anthelmintic therapy resulted in significantly increased systemic levels of type 1 and/or type 17 cytokines and in significantly decreased systemic levels of type 2 and regulatory (IL-10 and TGF-β) cytokines. In addition, anthelmintic therapy resulted in significantly increased TB antigen-stimulated levels of type 1 cytokines only. Our data therefore confirm that the modulation of systemic and TB antigen-stimulated cytokine responses in -LTB coinfection is reversible (for the most part) by anthelmintic treatment.
已知蠕虫感染可调节潜伏性结核病(LTB)中的细胞因子反应。然而,很少有研究探讨这种调节在驱虫治疗后是否可逆。我们测量了驱虫治疗前后LTB患者以及合并或不合并蠕虫感染的个体中1型、2型、17型和调节性细胞因子的全身水平以及经结核分枝杆菌(TB)抗原刺激后的水平。我们的数据显示,合并蠕虫感染的LTB患者全身和经TB抗原刺激后的1型(γ干扰素[IFN-γ]、肿瘤坏死因子α[TNF-α]和白细胞介素-2[IL-2])及17型(IL-17A和/或IL-17F)细胞因子水平显著降低,全身(而非经TB抗原刺激后)的2型(IL-4和IL-5)及调节性(转化生长因子β[TGF-β])细胞因子水平显著升高。驱虫治疗使1型和/或17型细胞因子的全身水平显著升高,2型及调节性(IL-10和TGF-β)细胞因子的全身水平显著降低。此外,驱虫治疗仅使经TB抗原刺激后的1型细胞因子水平显著升高。因此,我们的数据证实,驱虫治疗可(在很大程度上)逆转LTB合并感染中全身和经TB抗原刺激后的细胞因子反应调节。