Peters Nathan, Sacks David
Laboratory of Parasitic Diseases, NIAID, Bethesda, MD 20892-0425, USA.
Immunol Rev. 2006 Oct;213:159-79. doi: 10.1111/j.1600-065X.2006.00432.x.
Leishmania are digenetic protozoan parasites that are inoculated into the skin by vector sand flies, are taken up by macrophages, and produce a spectrum of chronic diseases in their natural reservoir and susceptible human hosts. During the early establishment of infection in the skin and lymphoid organs, Leishmania produce multiple effects on macrophage and dendritic cell functions that inhibit their innate anti-microbial defenses and impair their capacity to initiate T-helper 1 cell immunity. In addition, the skin is a site preconditioned for early parasite survival by virtue of a high frequency of steady-state, natural CD25+Foxp3+ regulatory T cells (Tregs) that function to suppress the generation of unneeded immune responses to infectious and non-infectious antigens to which the skin is regularly exposed. In murine models of infection, antigen-induced CD25+/-Foxp3-interleukin (IL)-10+ Treg cells act during the effector phase of the immune response to control immunopathology and may also delay or prevent healing. Finally, following resolution of infection in healed mice, CD25+Foxp3+ Tregs function in an IL-10-dependent manner to prevent sterile cure and establish a long-term state of functional immune privilege in the skin.
利什曼原虫是双宿主原生动物寄生虫，通过媒介白蛉接种到皮肤中，被巨噬细胞摄取，并在其天然宿主和易感人类宿主中引发一系列慢性疾病。在皮肤和淋巴器官感染初期，利什曼原虫对巨噬细胞和树突状细胞功能产生多种影响，抑制其天然抗菌防御能力，并损害其启动辅助性T细胞1型免疫的能力。此外，由于皮肤中稳态天然CD25+Foxp3+调节性T细胞（Tregs）的高频率存在，皮肤成为寄生虫早期存活的一个有利位点，这些调节性T细胞的作用是抑制对皮肤经常接触的传染性和非传染性抗原产生不必要的免疫反应。在小鼠感染模型中，抗原诱导的CD25+/-Foxp3-白细胞介素（IL）-10+调节性T细胞在免疫反应的效应阶段发挥作用，以控制免疫病理，还可能延迟或阻止愈合。最后，在治愈小鼠的感染消退后，CD25+Foxp3+调节性T细胞以IL-10依赖的方式发挥作用，防止无菌治愈，并在皮肤中建立长期的功能性免疫特权状态。
