Infection Immunology, Research Centre Borstel, D-23845 Borstel, Germany.
German Centre for Infection Research (DZIF), Partner Site Hamburg-Borstel-Lübeck-Riems, D-23845 Borstel, Germany.
Cells. 2020 Dec 15;9(12):2695. doi: 10.3390/cells9122695.
Protective immune responses to (Mtb) infection substantially depend on a delicate balance within cytokine networks. Thus, immunosuppressive therapy by cytokine blockers, as successfully used in the management of various chronic inflammatory diseases, is often connected with an increased risk for tuberculosis (TB) reactivation. Hence, identification of alternative therapeutics which allow the treatment of inflammatory diseases without compromising anti-mycobacterial immunity remains an important issue. On the other hand, in the context of novel therapeutic approaches for the management of TB, host-directed adjunct therapies, which combine administration of antibiotics with immunomodulatory drugs, play an increasingly important role, particularly to reduce the duration of treatment. In both respects, cytokines/cytokine receptors related to the common receptor subunit gp130 may serve as promising target candidates. Within the gp130 cytokine family, interleukin (IL)-6, IL-11 and IL-27 are most explored in the context of TB. This review summarizes the differential roles of these cytokines in protection and immunopathology during Mtb infection and discusses potential therapeutic implementations with respect to the aforementioned approaches.
保护性免疫应答对(Mtb)感染在很大程度上取决于细胞因子网络内的微妙平衡。因此,细胞因子阻滞剂的免疫抑制治疗,如在各种慢性炎症性疾病的治疗中成功应用,常与结核分枝杆菌(TB)再激活的风险增加有关。因此,寻找允许在不损害抗分枝杆菌免疫的情况下治疗炎症性疾病的替代疗法仍然是一个重要问题。另一方面,在管理 TB 的新型治疗方法的背景下,宿主导向的辅助治疗方法,将抗生素与免疫调节药物联合使用,发挥着越来越重要的作用,特别是可以减少治疗的持续时间。在这两方面,与共同受体亚基 gp130 相关的细胞因子/细胞因子受体可作为有前途的候选靶标。在 gp130 细胞因子家族中,白细胞介素(IL)-6、IL-11 和 IL-27 在 TB 方面的研究最多。本文综述了这些细胞因子在 Mtb 感染过程中的保护和免疫病理中的差异作用,并讨论了上述方法中潜在的治疗应用。