By Dr. Thomas Murooka, associate professor of immunology, Max Rady College of Medicine
It is well known that parasites have evolved strategies that permit their long-term survival in our bodies, many of them focused on evading recognition and removal by the host immune system.
Skin infections by the parasite Leishmania major, which are transmitted primarily through bites from an infected sandfly, are exceptionally well-suited at evading host immunity, with a small number of parasite-infected cells often remaining at the infection site long after the skin has healed. These residually infected cells have the potential to reinitiate disfiguring disease, called cutaneous leishmaniasis, if host immunity is later compromised, prompting questions into why our immune system is not able to completely clear these parasites in the first place.
In a collaborative study from immunology researchers at the University of Manitoba, led by recent PhD graduate Dr. Romaniya Zayats, we generated a new mouse model to systematically trace T cell responses against this parasitic infection using an experimental model of cutaneous leishmaniasis, now published in Nature Communications.
We provide direct evidence that regulatory T cells, normally present in the skin to prevent overt inflammation, play an important role in restraining host responses, leading to parasite survival in the skin. We described a new subset of these regulatory cells during Leishmania major infection and show that their removal reinvigorated host immune responses and helped clear these parasites.
Our studies highlight the complex evolutionary interplay between host and parasite populations that often controls disease severity and persistence and uncover new opportunities for therapeutic interventions against this neglected but life-threatening disease.
Dr. Zayats was supported by Research Manitoba and the University of Manitoba Graduate Fellowship for this work and has received numerous awards including the Mindel and Tom Olenick Research Award in Immunology, the Dr. Forough Khadem Memorial Award and travel awards to present at the American Association of Immunologists meetings in 2022 and 2023.
Dr. Jude Uzonna, professor of immunology, associate dean, research, Max Rady College of Medicine, and vice-dean, research, Rady Faculty of Health Sciences, and Dr. Thomas Murooka, associate professor of immunology, were co-senior authors on this study. We would like to thank all animal technicians, research support staff and veterinary services at the CACS for their assistance with these studies and their commitment to animal welfare.