Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
PLoS Negl Trop Dis. 2019 May 23;13(5):e0007436. doi: 10.1371/journal.pntd.0007436. eCollection 2019 May.
Despite worldwide mass drug administration, it is estimated that 68 million individuals are still infected with lymphatic filariasis with 19 million hydrocele and 17 million lymphedema reported cases. Despite the staggering number of pathology cases, the majority of LF-infected individuals do not develop clinical symptoms and present a tightly regulated immune system characterized by higher frequencies of regulatory T cells (Treg), suppressed proliferation and Th2 cytokine responses accompanied with increased secretion of IL-10, TGF-β and infection-specific IgG4. Nevertheless, the filarial-induced modulation of the host`s immune system and especially the role of regulatory immune cells like regulatory B (Breg) and Treg during an ongoing LF infection remains unknown. Thus, we analysed Breg and Treg frequencies in peripheral blood from Ghanaian uninfected endemic normals (EN), lymphedema (LE), asymptomatic patent (CFA+MF+) and latent (CFA+MF-) W. bancrofti-infected individuals as well as individuals who were previously infected with W. bancrofti (PI) but had cleared the infection due to the administration of ivermectin (IVM) and albendazole (ALB). In summary, we observed that IL-10-producing CD19+CD24highCD38dhigh Breg were specifically increased in patently infected (CFA+MF+) individuals. In addition, CD19+CD24highCD5+CD1dhigh and CD19+CD5+CD1dhighIL-10+ Breg as well as CD4+CD127-FOXP3+ Treg frequencies were significantly increased in both W. bancrofti-infected cohorts (CFA+MF+ and CFA+MF-). Interestingly, the PI cohort presented frequency levels of all studied regulatory immune cell populations comparable with the EN group. In conclusion, the results from this study show that an ongoing W. bancrofti infection induces distinct Breg and Treg populations in peripheral blood from Ghanaian volunteers. Those regulatory immune cell populations might contribute to the regulated state of the host immune system and are probably important for the survival and fertility (microfilaria release) of the helminth.
尽管在全球范围内进行了大规模药物治疗，但据估计，仍有 6800 万人感染淋巴丝虫病，报告的病例有 1900 万例鞘膜积液和 1700 万例淋巴水肿。尽管病理学病例数量惊人，但大多数感染 LF 的个体并未出现临床症状，表现出受严格调控的免疫系统，其特征是调节性 T 细胞（Treg）频率较高、增殖受到抑制和 Th2 细胞因子反应，同时伴有 IL-10、TGF-β 和感染特异性 IgG4 的分泌增加。然而，丝虫感染对宿主免疫系统的调节作用，特别是在持续的 LF 感染过程中调节性免疫细胞（如调节性 B 细胞（Breg）和 Treg）的作用，仍然未知。因此，我们分析了加纳未感染地方性正常人群（EN）、淋巴水肿（LE）、无症状带虫者（CFA+MF+）和潜伏感染（CFA+MF-）的沃氏线虫感染个体以及以前感染过沃氏线虫（PI）但因伊维菌素（IVM）和阿苯达唑（ALB）治疗而清除感染的个体外周血中的 Breg 和 Treg 频率。总的来说，我们观察到，在明显感染（CFA+MF+）个体中，产生 IL-10 的 CD19+CD24highCD38dhigh Breg 特异性增加。此外，CD19+CD24highCD5+CD1dhigh 和 CD19+CD5+CD1dhighIL-10+Breg 以及 CD4+CD127-FOXP3+Treg 的频率在沃氏线虫感染队列（CFA+MF+和 CFA+MF-）中均显著增加。有趣的是，PI 队列的所有研究调节性免疫细胞群体的频率水平与 EN 组相当。总之，本研究结果表明，加纳志愿者外周血中持续的沃氏线虫感染诱导了不同的 Breg 和 Treg 群体。这些调节性免疫细胞群体可能有助于宿主免疫系统的调节状态，并且可能对蠕虫的生存和生育力（微丝蚴释放）很重要。
