Institute of Immunology, University of Regensburg, Regensburg, Germany.
PLoS One. 2012;7(9):e44499. doi: 10.1371/journal.pone.0044499. Epub 2012 Sep 28.
Resistance to Leishmania major infection is dependent on the development of a cell-mediated Th1 immune response in resistant C57BL/6 mice whereas Th2-prone BALB/c mice develop non-healing lesions after infection. The chemokine receptor CCR6 is shared by anti-inflammatory regulatory T cells and pro-inflammatory Th17 cells. In a recent study we showed that C57BL/6 mice deficient in CCR6 exhibited enhanced footpad swelling and impaired T helper cell migration indicated by reduced recruitment of total T helper cells into the skin after infection and a reduced delayed type hypersensitivity reaction. Based on these findings we tested whether the lack of CCR6 alters Treg or Th17 cell responses during the course of Leishmania major infection. When we analyzed T cell subsets in the lymph nodes of CCR6-deficient mice, Th17 cell numbers were not different. However, reduced numbers of Treg cells paralleled with a stronger IFNγ response. Furthermore, the early increase in IFNγ-producing cells correlated with increased local tissue inflammation at later time points. Our data indicate an important role of CCR6 for Treg cells and a redundant role for Th17 cells in a Th1 cell-driven anti-parasitic immune response against Leishmania major parasites in resistant C57BL/6 mice.
抵抗利什曼原虫感染依赖于在抗性 C57BL/6 小鼠中发展细胞介导的 Th1 免疫应答，而倾向于 Th2 的 BALB/c 小鼠在感染后会发展为无法治愈的病变。趋化因子受体 CCR6 被抗炎调节性 T 细胞和促炎 Th17 细胞共享。在最近的一项研究中，我们发现 CCR6 缺陷的 C57BL/6 小鼠表现出增强的足垫肿胀和辅助性 T 细胞迁移受损，这表明在感染后总辅助性 T 细胞向皮肤的募集减少，迟发型超敏反应降低。基于这些发现，我们测试了缺乏 CCR6 是否会在利什曼原虫感染过程中改变 Treg 或 Th17 细胞反应。当我们分析 CCR6 缺陷小鼠淋巴结中的 T 细胞亚群时，Th17 细胞数量没有差异。然而，Treg 细胞数量减少与 IFNγ 反应增强相平行。此外，IFNγ 产生细胞的早期增加与后期局部组织炎症的增加相关。我们的数据表明 CCR6 对 Treg 细胞具有重要作用，而 Th17 细胞在抵抗性 C57BL/6 小鼠中针对利什曼原虫寄生虫的 Th1 细胞驱动的抗寄生虫免疫应答中具有冗余作用。
