National Centre for Cell Science, Ganeshkhind, Pune 411007, India.
Maulana Abul Kalam Azad University of Technology, BF142, Salt Lake City, Kolkata 700064, India.
Cytokine. 2018 Apr;104:110-113. doi: 10.1016/j.cyto.2017.10.005. Epub 2017 Oct 7.
Toll-like receptors (TLRs) recognize the pathogen-associated molecular patterns (PAMPs) and induce host-protective immune response. The role of the profilin-recognizing TLR11/TLR12 in Leishmania infection is unknown. Herein, we report that TLR11/ TLR12 expression increases in virulent L. major-infected macrophages but is prevented by miltefosine, an anti-leishmanial drug. While lipohosphoglycan (LPG) increases, LPG or TLR2 blockade prevents, the heightened TLR11/TLR12 expression. LPG-TLR2 interaction triggers MyD88- and TIRAP-mediated signaling enhancing ERK-1/2 activation and increased production of IL-10 that promotes TLR11/TLR12 expression. Profilin expression was higher in the virulent L. major and L. donovani parasites than that observed in the avirulent parasites. TLR11 or TLR12 silencing reduces parasite burden and increases IFN-γ, but reduces IL-4, production indicating that TLR11 and TLR12 play a pro-leishmanial role.
Toll 样受体 (TLRs) 识别病原体相关分子模式 (PAMPs)，并诱导宿主保护性免疫反应。丝氨酸蛋白酶抑制剂识别 TLR11/TLR12 在利什曼原虫感染中的作用尚不清楚。在此，我们报告 TLR11/TLR12 的表达在强毒力 L. major 感染的巨噬细胞中增加，但被 miltefosine（一种抗利什曼原虫药物）所阻止。虽然脂阿拉伯甘露聚糖 (LPG) 增加，但 LPG 或 TLR2 阻断可防止 TLR11/TLR12 的表达增加。LPG-TLR2 相互作用触发 MyD88 和 TIRAP 介导的信号转导，增强 ERK-1/2 的激活，并增加促进 TLR11/TLR12 表达的 IL-10 产生。在强毒力 L. major 和 L. donovani 寄生虫中，丝氨酸蛋白酶抑制剂的表达高于弱毒力寄生虫。TLR11 或 TLR12 的沉默可降低寄生虫负荷，并增加 IFN-γ 的产生，但降低 IL-4 的产生，表明 TLR11 和 TLR12 发挥促利什曼原虫的作用。
