Tuero Iskra, Palma Sandra, Cabeza Franco, Saleemi Sarah, Rodriguez Silvia, Gonzales Isidro, Mayta Holger, Mahanty Siddhartha, Garcia Hector H, Gilman Robert H
Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú
Asociación Benéfica PRISMA, Lima, Perú
PLoS Negl Trop Dis. 2015 Oct 27;9(10):e0004143. doi: 10.1371/journal.pntd.0004143. eCollection 2015 Oct.
The ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.
Peripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg.
Sera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-γ/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1β/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-β secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls.
CONCLUSIONS/SIGNIFICANCE: T. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.
猪带绦虫调节免疫系统的能力可能有助于其在人类宿主体内长期存活。我们检验了免疫反应的性质与寄生虫位置及感染临床表现相关的假说。
从未经治疗的神经囊尾蚴病(NCC)患者中获取外周血单个核细胞(PBMC),这些患者根据囊肿仅存在于脑实质内或蛛网膜下腔而被分类为实质感染或蛛网膜下腔感染,同时从年龄和性别与每位患者匹配的未感染(对照)个体中获取PBMC。使用多重检测技术,检测NCC患者和对照的血清以及猪带绦虫抗原(TsAg)刺激后PBMC产生的细胞因子,以测定炎性和调节性细胞因子的水平。通过流式细胞术对PBMC进行体外表型分析以及在TsAg体外刺激后进行表型分析。
实质型NCC患者的血清显示出比蛛网膜下腔型NCC患者显著更高的Th1(IFN-γ/IL-12)和Th2(IL-4/IL-13)细胞因子反应,并且IL-1β/IL-8/IL-5水平有升高趋势。在实质型NCC患者的PBMC上清液中检测到的体外抗原驱动的TNF-β分泌也高于蛛网膜下腔型NCC患者。相比之下,蛛网膜下腔型NCC患者对TsAg刺激的IL-10反应显著高于实质型NCC患者。尽管在体外未发现调节性T细胞(Tregs)频率存在差异,但在将数据针对相应对照进行标准化后,蛛网膜下腔型NCC患者在TsAg刺激后Tregs的扩增趋势大于实质型NCC患者。
结论/意义:与实质感染相比,蛛网膜下腔的猪带绦虫感染与增强的调节性免疫反应相关。由此产生的抗炎环境可能代表寄生虫维持宿主体内宽松环境或减少宿主免疫反应对中枢神经系统造成炎性损伤的一种策略。