Authors

J Furlong-Silva¹; S D Cross¹; N Pionnier¹; A Steven¹; M J Taylor¹; J D Turner¹;  ¹ Liverpool School of Tropical Medicine

Discussion

Lymphatic Filariasis (LF) is the second leading cause of global disability, with an estimated 40 million suffering severe disease in the form of secondary lymphoedema and elephantiasis. Novel anti-morbidity strategies are required to alleviate life-long morbidity in these individuals which persists beyond elimination of LF transmission. Lymphatic remodelling, following infection, is implicated in development of disease, although its role in pathology and how it is induced remains poorly understood. In this study, an Intravital imaging technique was used to image the lymphatics of a mouse filarial leg infection model for 5 weeks following infection, in immunocompetent and severe-combined immunodeficient (SCID) 10 mouse cohorts. Interestingly, lymphatic remodelling was observed frequently and as little as 2 weeks following infection. Qualitative analysis suggested the immunocompetent mouse cohort displayed a higher degree of remodelling compared to SCID (7 compared to 4). The data suggests lymphatic remodelling is a significant, early event after infection, which we term ‘covert pathology’. Furthermore, early data suggests the host adaptive immune response contributes to the remodelling process. Future work is required to investigate the adaptive and innate immune mechanisms involved in the induction of lymphatic remodelling, following filarial infection. Such work could yield anti-morbidity therapeutic target pathways for early-stage LF pathology patients.