Roye O, Delhem N, Trottein F, Remoué F, Nutten S, Decavel J P, Delacre M, Martinot V, Cesbron J Y, Auriault C, Wolowczuk I
Centre National de la Recherche Scientifique, Unité de Recherche Associée 1854, Institut de Biologie de Lille, France.
J Immunol. 1998 Oct 15;161(8):4161-8.
The parasite Schistosoma mansoni infects its definitive mammalian host through an obligatory cutaneous penetration. In this work, we studied early immune response following migration of larvae through human skin, the first immunocompetent organ encountered by the parasite. For this purpose we used an experimental model of severe combined immunodeficient mice engrafted with human skin and injected with autologous PBL. Six days after percutaneous infection, we observed an infiltration of lymphocytes within the human skin, predominantly composed of CD4+ T cells. Moreover, among the cytokines potentially present in the infected skin, immunohistochemistry analysis revealed an in vivo expression of IL-7 in the epidermal layers and strikingly at the level of vascular endothelium. Using an in vitro coculture system, we showed that the S. mansoni larvae directly trigger IL-7 production by human dermal microvascular endothelial cells but not by keratinocytes. Finally, measurements of IL-7 concentrations in plasma of 187 S. mansoni-infected individuals showed that the youngest, which are also the most infected, displayed the highest IL-7 levels. Together, these findings describe dermal endothelial cells as a novel source of IL-7, a cytokine particularly important in schistosomiasis.
曼氏血吸虫通过皮肤的必经穿透感染其终末哺乳动物宿主。在这项研究中,我们研究了幼虫穿过人体皮肤(寄生虫遇到的首个具有免疫活性的器官)后早期的免疫反应。为此,我们使用了一种实验模型,即严重联合免疫缺陷小鼠移植人皮肤并注射自体外周血淋巴细胞。经皮感染6天后,我们观察到人体皮肤内有淋巴细胞浸润,主要由CD4 + T细胞组成。此外,在感染皮肤中可能存在的细胞因子中,免疫组织化学分析显示白细胞介素-7(IL-7)在表皮层中,尤其是在血管内皮水平有体内表达。使用体外共培养系统,我们发现曼氏血吸虫幼虫直接触发人真皮微血管内皮细胞产生IL-7,而角质形成细胞则不会。最后,对187名曼氏血吸虫感染个体血浆中IL-7浓度的测量表明,年龄最小且感染最严重的个体IL-7水平最高。这些发现共同表明真皮内皮细胞是IL-7的新来源,IL-7是一种在血吸虫病中特别重要的细胞因子。