Katawa Gnatoulma, Layland Laura E, Debrah Alex Y, von Horn Charlotte, Batsa Linda, Kwarteng Alexander, Arriens Sandra, W Taylor David, Specht Sabine, Hoerauf Achim, Adjobimey Tomabu
Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany; Advanced School of Medical Biology and Food Technology (ESTBA), University of Lomé, Lomé, Togo.
Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
PLoS Negl Trop Dis. 2015 Jan 8;9(1):e3414. doi: 10.1371/journal.pntd.0003414. eCollection 2015 Jan.
Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4+ T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4+CD25hiFoxp3+ regulatory T cells. These profiles included increased IL-17A+, IL-4+, RORC2+ and GATA3+CD4+ T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis.
盘尾丝虫病的临床表现从全身性盘尾丝虫病（GEO）到罕见但严重的高反应性（HO）/sowda型不等。由于疾病发病机制与宿主炎症反应相关，我们研究了Th17反应是否与HO中加重的病理状况有关。我们使用流式细胞术、丝虫特异性细胞因子反应和PCR阵列，比较了呈现两种极端感染形式的个体以及地方性正常人（EN）的免疫细胞谱，包括Th亚群。除了记忆性CD4+T细胞频率升高外，HO患者还表现出Th17和Th2谱增强，但CD4+CD25hiFoxp3+调节性T细胞减少。这些谱包括IL-17A+、IL-4+、RORC2+和GATA3+CD4+T细胞群体增加。由于Th17相关基因（IL-17家族成员、IL-6、IL-1β和IL-22）和Th2相关基因（IL-4、IL-13、STAT6）在HO个体中均显著上调，因此使用PCR阵列进一步证实了流式细胞术数据。此外，与GEO或EN组相比，在体外观察到高反应性个体中盘尾丝虫特异性Th2反应更强，尤其是IL-13。这项研究提供了初步证据，表明Th17和Th2细胞频率升高是促使严重盘尾丝虫病发展的免疫网络的一部分。
