Chessler Anne-Danielle C, Unnikrishnan Meera, Bei Amy K, Daily Johanna P, Burleigh Barbara A
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston MA 02115, USA.
J Immunol. 2009 Feb 15;182(4):2288-96. doi: 10.4049/jimmunol.0800621.
Early interactions between the protozoan parasite Trypanosoma cruzi and mammalian hosts at primary sites of infection (skin and mucosal membranes) are predicted to be critical determinants of parasite survival and dissemination in the host. To investigate the early host response triggered by three different strains of T. cruzi at a local infection site, changes in host gene expression were monitored in a murine intradermal infection model using Affymetrix oligonucleotide arrays. Robust induction of IFN-stimulated genes was observed in excised skin 24 h postinfection where the level of IFN-stimulated gene induction was parasite strain-dependent, with the least virulent strain triggering a muted IFN response. Infection of mice immunodepleted of IFN-gamma-producing cells or infection of IFN-gamma-deficient mice had minimal impact on the IFN response generated in T. cruzi-infected mice. In contrast, infection of mice lacking the type I IFN receptor demonstrated that type I IFNs are largely responsible for the IFN response generated at the site of infection. These data highlight type I IFNs as important components of the innate immune response to T. cruzi at the site of inoculation and their role in shaping the early transcriptional response to this pathogen.
原生动物寄生虫克氏锥虫与哺乳动物宿主在主要感染部位（皮肤和粘膜）的早期相互作用预计是寄生虫在宿主体内存活和传播的关键决定因素。为了研究由三种不同克氏锥虫菌株在局部感染部位引发的早期宿主反应，使用Affymetrix寡核苷酸阵列在小鼠皮内感染模型中监测宿主基因表达的变化。感染后24小时在切除的皮肤中观察到干扰素刺激基因的强烈诱导，其中干扰素刺激基因诱导水平取决于寄生虫菌株，毒性最小的菌株引发的干扰素反应较弱。对缺乏产生干扰素-γ细胞的小鼠进行免疫耗竭感染或对干扰素-γ缺陷小鼠进行感染，对克氏锥虫感染小鼠产生的干扰素反应影响最小。相比之下，对缺乏I型干扰素受体的小鼠进行感染表明，I型干扰素在很大程度上负责在感染部位产生的干扰素反应。这些数据突出了I型干扰素作为接种部位对克氏锥虫先天免疫反应的重要组成部分及其在塑造对该病原体的早期转录反应中的作用。
