Unraveling the Dynamics of Human Filarial Infections: Immunological Responses, Host Manifestations, and Pathogen Biology.

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.