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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.
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1 Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA; Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
2 UMR7245, MCAM, Museum national d’Histoire naturelle, Paris, France
3 Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
4 Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Glasgow, UK
5 Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA; Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA