Nematodes share a set of skills that allow them to move within the mud, sand, or collagenous tissue. The eventual invasion of skin lymphatics is an inevitable consequence of weak elastic support and sufficiently large lumen of lymphatics
Published in Microbiology

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What began with a supposedly quick experimental verification of a question relevant in a field of filarial parasitology soon turned into a fascinating story culminated with a set of discoveries that may impact disciplines, from human pathology and vaccination to filaria ecology and the evolution of parasitism. 

After initial experiments, we knew that infective migratory larvae of Litomosoides sigmodontis, a popular filaria model of mouse pleural filariasis, exclusively use the lymphatics, but not the blood vessels, during migration from the skin to their breeding destination in the cavity that surrounds the lungs. If we were to dig deeper into the mechanism behind that behavior, we should use techniques that allow, for instance, imaging of millimeters-long nematode parasite migration in the live skin. Because there were no such methods at hand, we were looking at a brand new goal, that is, the development of imaging methodology from scratch, the approach that generally requires dedication and time. Luckily, our lab always valued the freedom of research, even when it meant initiating a high-risk project with, as in this case, no clear end-date and definitely, no guarantee for success. In years to follow, this attitude drove the generation of methods that produced some of the most surprising results. 

How is it possible that nematodes can navigate with such a precision to distant locations within our bodies?

Depending on the parasite, its infective larvae that entered the skin can remain in the dermis or subcutaneous tissue, or escape the skin and settle in lymphatics or peritoneal cavity, or continue their journey via blood vessels to the heart. Their migration must end at the lungs, which blood capillaries function as a filtration station. And so, parasitic larvae reaching lung capillaries must exit either into the pleural cavity, or move over the surface of bronchi towards the intestine. Only accidentally, parasites cause serious illnesses when their larvae end up in one of the capillary beds of the central blood circulation, for example, in the kidney, brain, meninges, or the eye.

Paradoxically, this diversity of locations (habitats) that can be colonized by parasitic nematodes is paralleled by morphologic and functional austerity of their infective larvae, which shared body plan, a sausage-shaped balloon that can move only with side-to-side sinusoidal bending motion, provides little room for functional modifications. Nematodes are also unable to sense the chemokine gradients, the native navigation systems of vertebrate tissues, while their environmental receptors are ineffective within tissues that are kept under relatively even physicochemical conditions.

Yet, the parasitic nematodes have an ingenious way to navigate within the host. We found that the essential abilities that allow nematodes to move across the granular materials, such as sand or soil, also predispose them for migration in a similar gelly environment of the skin. The eventual invasion of lymphatic collecting vessels is the inevitable consequence of weak elastic support of lymphatics wall enclosing optimal for nematode migration lumens. Once within lymphatics that should be roughly three times the diameter of infective larvae, parasitic nematodes can move preferentially downstream towards blood circulation using the same movement that was evolutionarily optimized for crossing granular materials. Alone our findings do not explain the attraction of infective filariae to specific body cavities (Supplementary discussion). However, the explanation becomes apparent when we correlate the final location of the adults to their developmental parameters, primarily, the diameter of infective larvae and the day they undergo molting. Therefore, too large parasite (e.g., larvae of Loa Loa) would be unable to enter smaller lymphatics and should remain in the subcutaneous space, while the majority of parasites that are fit to embark the lymphatic escape route leading to lungs capillary circulation, will experience the advantage of systemic spread. Their journey can be terminated anywhere along this route by the sudden body enlargement during the molting event, that is when larvae become too large for further migration. Together with the lymphatic collectors serving as the universal systemic entry gate, these simple developmental modifications should be sufficient for nematode parasites to enter and exit the lymphatic expressway at specific locations within the host but also to switch between different hosts.

Figure 1. Bacterivorous soil-derived (non-parasitic) nematode (red) wrapped around a nerve in the mouse skin. Nerves, blood vessels, and lymphatics of the skin are stained green.
Figure 1. Bacterivorous soil-derived (non-parasitic) nematode (red) wrapped around a nerve in the mouse skin. Nerves, blood vessels, and lymphatics are stained green

Non-parasitic nematodes also can migrate in the skin and spread via lymphatic

What became apparent is that most if not all, nematodes share a set of skills that allow them to efficiently migrate in various non-liquid environments, such as, mud, sand, but also collagenous tissues. Therefore, any soil bacterivorous or predatory nematode that finds itself in the skin (e.g., through a contaminated skin wound) should be able to migrate within the dermis, and if it has the right morphological parameters, should be able to invade lymphatics. As the eventual lymphatic invasion and subsequent systemic spread is an unavoidable consequence of the unique anatomy of lymphatics, there should be no selective pressures for parasites to explore dissemination alternatives, for example, vessels of the blood circulation. From this perspective, it might be less of a surprise that despite a long history of parasitic interactions between nematodes and vertebrates, no defense mechanism evolved to protect lymphatics against the parasitic invasion. Therefore, with minimal impact on the animal fitness, entrapment of parasitic nematodes by skin lymphatics might serve as a pre-emptive defense strategy preventing the evolution of adaptations such as, a mechanism for direct blood vessel invasion, which would likely increase the rate of systemic embolisms or meningeal-encephalitic infections.

*Inherent biomechanical traits enable infective filariae to disseminate through collecting lymphatic vessels. Witold W. Kilarski, Coralie Martin, Marco Pisano, Odile Bain, Simon A Babayan & Melody A. Swartz. Nat Commun. (2019)  (

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