Department of Medicine, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
J Leukoc Biol. 2010 Aug;88(2):227-32. doi: 10.1189/jlb.0809550. Epub 2010 Mar 18.
In the present study, we dissected the pathways that trigger the IL-17A responses by MTB. Dectin-1 and TLR4 were shown to be involved in MTB-induced IL-17A production, and blockade of the NOD2, TLR2, or MR had no effect on IL-17A. The MAPK Erk, known to mediate transcription of IL-1beta mRNA, was strongly involved in the IL-17A production induced by MTB. The intracellular enzymes caspase-1 and serine proteases, which process pro-IL-1beta into the active IL-1beta, were also crucial for the induction of IL-17A. Lastly, the MTB-induced IL-17A response was strongly dependent on signaling through the IL-1R but not the IL-6R pathway. In conclusion, the MTB-induced IL-17A response relies strongly on the endogenous IL-1 pathway and IL-1R signaling. TLR4 and dectin-1 are the main receptors responsible for mediating the signals responsible for IL-17A production by MTB. These findings contribute to a better understanding of the host response to mycobacteria and provide the opportunity to explore potential, novel, therapeutic strategies against TB.
在本研究中，我们剖析了 MTB 触发 IL-17A 反应的途径。Dectin-1 和 TLR4 被证明参与了 MTB 诱导的 IL-17A 产生，而 NOD2、TLR2 或 MR 的阻断对 IL-17A 没有影响。MAPK Erk 已知介导 IL-1beta mRNA 的转录，强烈参与了 MTB 诱导的 IL-17A 产生。细胞内酶半胱天冬酶-1 和丝氨酸蛋白酶，将前体 IL-1beta 加工成活性的 IL-1beta，对于诱导 IL-17A 也至关重要。最后，MTB 诱导的 IL-17A 反应强烈依赖于通过 IL-1R 而不是 IL-6R 途径的信号转导。总之，MTB 诱导的 IL-17A 反应强烈依赖于内源性的 IL-1 途径和 IL-1R 信号转导。TLR4 和 dectin-1 是主要的受体，负责介导 MTB 产生 IL-17A 的信号。这些发现有助于更好地理解宿主对分枝杆菌的反应，并为探索针对结核病的潜在新的治疗策略提供了机会。
