Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Clinic Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
Microbes Infect. 2010 Jul;12(7):555-64. doi: 10.1016/j.micinf.2010.03.011. Epub 2010 Mar 30.
Transforming growth factor-beta (TGF-beta) is a key cytokine in immune regulation, cell differentiation, development, wound healing, and tissue remodelling. It mediates immunosuppression in filarial infections facilitating parasite persistence, while attenuating immunopathology, which is induced by migrating microfilariae. Immunosuppression rises with parasite burden, but it remains unknown whether filariae elicit local release of immunosuppressive cytokines. Therefore, using immunohistology, we investigated the expression of stable, released latent TGF-beta1 in subcutaneous nodules from highly infected, hyporeactive onchocerciasis patients, harbouring adult Onchocerca volvulus. Since many cell types produce TGF-beta, we elucidated the cellular source, distribution and dependency on the worms' sex, productivity and vitality. We found TGF-beta1 to be abundantly expressed by T cells, plasma/B cells, macrophages, mast cells, fibrocytes, and vascular endothelial cells, particularly in onchocercomas with productive or previously productive females, damaged, dead and resorbed adult worms or microfilariae. We conclude TGF-beta to be antigen induced by the filariae since expression was scarce around subcutaneous arthropods or cholesterol crystals in onchocercomas. Enhanced expression after ivermectin or endobacteria-depleting doxycycline treatment indicates induction to depend on filariae and not on Wolbachia endobacteria. TGF-beta(+) cells were reduced in HIV co-infection. This finding of local and sustained TGF-beta induction by vital and dead filariae, untreated and after treatment, adds new aspects to immunomodulation by helminths.
转化生长因子-β（TGF-β）是免疫调节、细胞分化、发育、伤口愈合和组织重塑的关键细胞因子。它在丝虫感染中介导免疫抑制，促进寄生虫的持续存在，同时减轻由迁移的微丝蚴引起的免疫病理学。免疫抑制随着寄生虫负担的增加而增加，但尚不清楚丝虫是否会引发局部释放免疫抑制细胞因子。因此，我们使用免疫组织化学方法研究了皮下结节中稳定释放的潜伏 TGF-β1 在高度感染、低反应性盘尾丝虫病患者中的表达，这些患者体内存在成年盘尾丝虫。由于许多细胞类型产生 TGF-β，我们阐明了细胞来源、分布以及对蠕虫性别、生殖力和活力的依赖性。我们发现 TGF-β1 大量表达于 T 细胞、浆细胞/ B 细胞、巨噬细胞、肥大细胞、成纤维细胞和血管内皮细胞，特别是在具有生殖力或以前具有生殖力的雌性、受损、死亡和吸收的成年蠕虫或微丝蚴的盘尾丝虫病中。我们得出结论，TGF-β 是由丝虫诱导产生的，因为在盘尾丝虫病中的皮下节肢动物周围或盘尾丝虫病中的胆固醇晶体周围表达很少。伊维菌素或去除内共生菌的强力霉素治疗后表达增强表明诱导依赖于丝虫而不是沃尔巴克氏体内共生菌。在 HIV 合并感染中，TGF-β(+)细胞减少。这一发现表明，有活力和死亡的丝虫、未经治疗和治疗后，都会在局部持续诱导 TGF-β，这为寄生虫的免疫调节增加了新的方面。
