Rajamanickam Anuradha, Babu Subash
National Institute of Allergy and Infectious Diseases, National Institutes of Health-International Center for Excellence in Research, Chennai 600031, India.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Pathogens. 2025 Feb 25;14(3):223. doi: 10.3390/pathogens14030223.
Lymphatic filariasis (LF), or elephantiasis, is a neglected tropical disease caused by filarial worms, primarily , transmitted through mosquito bites. It often begins in childhood but may not show symptoms until later, leaving many individuals asymptomatic for long periods. LF disrupts the lymphatic system, causing severe swelling in the limbs and genitals, leading to deformities and disabilities. The World Health Organization estimates that around 51 million people are affected globally, with 36 million suffering from chronic conditions like lymphedema and hydrocele. In 2021, approximately 882.5 million people in 44 countries required preventive chemotherapy, making LF the second leading parasitic cause of disability, significantly impacting socioeconomic status. The immune response to filarial parasites is complex, involving both innate and adaptive immune cells. A key feature of LF immunology is the antigen-specific Th2 response, expansion of IL-10-producing CD4 T cells, and a muted Th1 response. This T cell hypo-responsiveness is crucial for sustaining long-term infections with high parasite densities. While the correlates of protective immunity are not fully understood-due in part to a lack of suitable animal models-T cells, particularly CD4 Th2 cells, and B cells, play essential roles in immune protection. Moreover, host immune responses contribute to the disease's pathological manifestations. A failure to induce T cell hypo-responsiveness can lead to exaggerated inflammatory conditions such as lymphedema, hydrocele, and elephantiasis. Filarial infections also induce bystander effects on various immune responses, impacting responses to other infectious agents. This intricate immune interplay offers valuable insights into the regulation of immune responses to chronic infections. This review explores recent immunological research on lymphatic filarial worms, highlighting their effects on both innate and adaptive immune responses in humans and the mechanisms underlying this neglected tropical disease.
淋巴丝虫病（LF），又称象皮病，是一种由丝虫引起的被忽视的热带病，主要通过蚊虫叮咬传播。它通常始于儿童期，但可能直到后期才出现症状，许多人会长期无症状。LF会破坏淋巴系统，导致四肢和生殖器严重肿胀，进而造成畸形和残疾。世界卫生组织估计，全球约有5100万人受其影响，其中3600万人患有淋巴水肿和鞘膜积液等慢性病。2021年，44个国家约8.825亿人需要接受预防性化疗，这使LF成为导致残疾的第二大寄生虫病因，对社会经济地位产生重大影响。对丝虫寄生虫的免疫反应很复杂，涉及先天免疫细胞和适应性免疫细胞。LF免疫学的一个关键特征是抗原特异性Th2反应、产生IL-10的CD4 T细胞扩增以及减弱的Th1反应。这种T细胞低反应性对于维持高寄生虫密度的长期感染至关重要。虽然保护性免疫的相关因素尚未完全了解——部分原因是缺乏合适的动物模型——但T细胞，尤其是CD4 Th2细胞和B细胞，在免疫保护中发挥着重要作用。此外，宿主免疫反应会导致该疾病的病理表现。无法诱导T细胞低反应性会导致如淋巴水肿、鞘膜积液和象皮病等过度炎症状态。丝虫感染还会对各种免疫反应产生旁观者效应，影响对其他感染因子的反应。这种复杂的免疫相互作用为慢性感染免疫反应的调节提供了有价值的见解。本综述探讨了近期关于淋巴丝虫的免疫学研究，重点介绍了它们对人类先天免疫和适应性免疫反应的影响以及这种被忽视的热带病的潜在机制。
