Abstract
Filariases are diseases caused by arthropod-borne filaria nematodes. The related pathologies depend on the location of the infective larvae when their migration, the asymptomatic and least studied phase of the disease, comes to an end. To determine factors assisting in filariae dissemination, we image Litomosoides sigmodontis infective larvae during their escape from the skin. Burrowing through the dermis filariae exclusively enter pre-collecting lymphatics by mechanical disruption of their wall. Once inside collectors, their rapid and unidirectional movement towards the lymph node is supported by the morphology of lymphatic valves. In a microfluidic maze mimicking lymphatic vessels, filariae follow the direction of the flow, the first biomechanical factor capable of helminth guidance within the host. Finally, non-infective nematodes that rely on universal morpho-physiological cues alone also migrate through the dermis, and break in lymphatics, indicating that the ability to spread by the lymphatic route is an ancestral trait rather than acquired parasitic adaptation.
Highlights
Filariases are diseases caused by arthropod-borne filaria nematodes
The reproductive filaria worms can dwell in collecting lymphatic vessels for 15 years, and despite impairment to lymphatic contractility and the valve function, their presence leads to lymphangiectasis, the enlargement of collecting vessels, and markedly enhanced lymph flow, the cardinal signs of lymphatic filariasis[3,4]
These results show that infective larvae can localize and invade lymphatic vessels and reach the draining lymph nodes (LN) within minutes after entering the skin (Supplementary Note 10)
Summary
Filariases are diseases caused by arthropod-borne filaria nematodes. The related pathologies depend on the location of the infective larvae when their migration, the asymptomatic and least studied phase of the disease, comes to an end. Even the requirement of lymphatic vessels for migration of Litomosoides sigmodontis, a commonly used rodent model of nonlymphatic filariasis, remains speculative[15,16] These earliest migratory events in filarial infection are challenging to study due in part to technical shortcomings of genetic manipulations of helminths that impede the use of standard imaging techniques in animals[17]. A method of fluorescent labeling of live filariae, combined with adapted imaging techniques—intravital epifluorescence, confocal optical sectioning of whole-mounted skin[20,21,22], and near-infrared macroscopy—allow us to analyze processes that have not previously been visualized in a live animal This includes migration of infective larvae within the skin, invasion of precollecting lymphatic vessels, and subsequent intralymphatic escape to the LN. This suggests that the ability of filariae to invade lymphatics and colonize the host is an ancestral or symplesiomorphic trait shared at least by filariae and free-living nematodes, that is, the majority of zooparasitic and terrestrial nematodes[24]
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