Immunomodulation in chronic Loiasis: a double-edged sword?
Final Report Abstract
How is the immune system effected in patients with chronic loiasis infections? Loiasis is a parasitic disease caused by worms called Loa loa, which are transmitted from one patient to another by the bites of deer flies. The disease is also known as ‘eye-worm’, because the adult worms, which can live for over 10 years and migrate around patients’ bodies just below the skin, can sometimes be seen crossing the eye. The disease occurs only in Central Africa, where it nevertheless effects more than 10 million people. Despite this, the disease has been so neglected by the scientific and health community that it doesn’t even feature on the World Health Organization’s official list of Neglected Tropical Diseases. Patients with chronic loiasis have surprisingly few symptoms normally associated with infections, such as fever. This suggests that these parasitic worms exert strong pressure on patients’ immune systems in order to suppress immunity that might otherwise kill or expel the worms. At first that might sound like a win-win situation, but it has been shown loiasis in fact still causes a significant burden of disease and even increases patients’ chances of dying. In addition, loiasis may also suppress beneficial immune responses against other common infectious diseases and the response to vaccines. When loiasis patients with very high numbers of young worms are treated with certain drugs to kill these parasites, however, their immune systems can sometimes overreact so badly that the patient dies. Very little is understood about these two extremes of how the immune system is affected in patients with chronic loiasis infections – a proverbial ‘double-edged sword’. In this project, we set out to study exactly this in Gabon, a country in Central Africa with a very high burden of loiasis. We took blood samples from a cross-section of the population, infected-or-not with loiasis, as well as from loiasis patients who were being treated with different combinations of drugs against the parasite. We studied various types of white blood cells thought to be involved in activating the immune system (in particular so-called eosinophils) or suppressing the immune system (so called myeloid-derived suppressor cells (MDSCs) and regulatory T-cells). We show, not wholly surprisingly, that eosinophils play a role in the increased activation of the immune system in patients during drug treatment of loiasis. More interestingly, these cells also appear to be more common and more activated even in patients with chronic loiasis patients who are not being treated and have relatively few symptoms. Somewhat to our surprise we did not find higher numbers of MDSCs in patients with chronic loiasis infections, although we did show that those MDSCs that are present can indeed suppress other parts of the immune system. Work is currently still ongoing to see if instead regulatory T-cells are the main white blood cells responsible for suppressing immunity in patients with chronic loiasis infections. Importantly, we furthermore confirmed the hypothesis that loiasis also causes suppression of immunity against other bugs that cause disease, such as some bacteria. This project also provided the opportunity to a number of talented young African scientists to further develop their research skills and obtain degrees which will help them progress their promising careers. As part of this project, we were moreover granted the means to organise the first ever workshop on immunology in Central Africa. In future, it would be very interesting to continue studying in more detail the white blood cells that suppress immunity in patients with chronic loiasis. This knowledge could lead to the development of treatments to not only help patients to clear their loiasis infections more effectively, but also to respond better to other infectious diseases and vaccines. Finally, applying this knowledge in reverse might eventually even prove beneficial in patients with a completely different type of disease, who suffer from unwanted overactivation of their immune system.
Publications
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Eosinophils, basophils and myeloid-derived suppressor cells in chronic Loa loa infection and its treatment in an endemic setting. PLOS Neglected Tropical Diseases, 18(5), e0012203.
Burger, Gerrit; Adamou, Rafiou; Kreuzmair, Ruth; Ndoumba, Wilfrid Ndzebe; Mbassi, Dorothea Ekoka; Mouima, Anne Marie Nkoma; Tabopda, Carole Mamgno; Adegnika, Roukoyath Moyoriola; More, Ayong; Okwu, Dearie Glory; Mbadinga, Lia-Betty Dimessa; Calle, Carlos Lamsfus; Veletzky, Luzia; Metzger, Wolfram Gottfried; Mordmüller, Benjamin; Ramharter, Michael; Mombo-Ngoma, Ghyslain; Adegnika, Ayola Akim; Zoleko-Manego, Rella & McCall, Matthew B. B.
