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Studies highlight role of skin in fly-borne disease

Research underlines the importance of the route of infection for sleeping sickness parasites.

Tryps eGFP
The parasites are controlled by antibodies produced in the spleen

New discoveries focused on how the parasites that cause sleeping sickness are introduced into the body could help inform the search for new treatments.

Researchers have sought to better understand the significance of the skin as the point of entry into the body for African trypanosome parasites, which until now has been an overlooked area of research.

Their study of infections of trypanosomes, which spread through the bite of tsetse flies, has highlighted a critically important role for the spleen in the immune response to parasites transferred via the skin.

A separate review of research by the same team has underscored that the skin may play a role in influencing disease outcomes.

Both studies could inform the search for new therapies for sleeping sickness, which causes widespread disease in people and livestock. It represents a risk to millions of people and animals in sub-Saharan Africa, and without treatment can be fatal.

Antibody production

Research in mice examined how the immune system in mammals responds to parasites when they are introduced via the skin.

Previous research has shown that after trypanosomes enter the skin, they accumulate within the draining lymph nodes, before spreading to the bloodstream and around the body.

However, the latest study found that when the lymph nodes were absent, sleeping sickness infection was still able to take hold throughout the blood and body, contrary to what was expected.

In addition, animals with healthy spleens and others without functioning spleens responded similarly to a first wave of parasite infection reaching the bloodstream, during the early stages of disease.

However, mice with unhealthy spleens were unable to produce the necessary antibodies to control subsequent waves of parasites recirculating in the blood.

The findings suggest that the initial wave of infection is met by unspecific antibodies, perhaps in combination with an immune response in the skin and draining lymph nodes.

Subsequent waves of infection, caused by the parasites circulating in the bloodstream, are better controlled by specialised antibodies produced by the spleen.

Complex response

In a review of studies relating to infections caused by bites to the skin, researchers underscored the need to understand the immune response in the skin and beyond, as the parasites travel towards the bloodstream from the skin.

Until recently, few studies considered the impact of the skin as a point of entry for the parasites, and how this might affect development of the resulting infection.

Recent studies have also highlighted that parasites can remain in the skin - but it is not clear if these are sub-populations distinct from those found in the blood, or if parasites travel between both organs, and what effect these have on the resulting infection.

Both studies were carried out by a team of Roslin scientists and published in the journal Frontiers in Immunology.

Sleeping sickness is not just a disease of the lymphatic and circulatory systems, but is also a disease of the skin – it is imperative that we gain a full understanding of how the infection affects the body and the immune response invoked, in order to find the best ways to control the disease.

Dr Omar AlfituriResearch Fellow, the Roslin Institute

** The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. **

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Image credit: Omar Alfituri