Our lab studies the immune response to filariae, tissue-invasive roundworms transmitted by arthropods. Filariae are parasitic organisms that cause devastating diseases throughout the tropics. Pathogenic human filariae include Wuchereria bancrofti and Brugia malayi, which cause lymphatic filariasis, Onchocerca volvulus, the causative agent of river blindness, and Loa loa, which causes African eyeworm. Lymphatic filariasis alone infects approximately 100 million people worldwide and causes painful and disfiguring manifestations such as genital swelling and lymphedema in over 40 million of these individuals. Onchocerciasis infects between 30 and 40 million people, causing skin disease in most and blindness or severe visual impairment in almost one million, mostly in sub-Saharan Africa. Because these diseases maim, but do not kill, they cause lifelong suffering and are a leading cause of morbidity worldwide.
The immune response to filariae is markedly different than that to most viral, bacterial, and fungal infections. Like other helminths, filariae induce a type 2 immune response characterized by eosinophilia, elevated serum levels of Ag-specific and polyclonal IgE, and increases in T-cell production of IL-4, IL-5, and IL-13. When a person is infected for a long time, however, the immune response to filarial worms diminishes, though the rest of the immune system continues to function against other infections. While it is clear that IL-4 plays a central role in driving type 2 responses, the exact factors responsible for the initiation, maintenance, and eventual diminution of the Th 2 immune response in filarial infections remain unknown. Recent studies from our group have demonstrated that basophils function to amplify type 2 immune responses and that the immunoregulation induced by chronic filarial infection does not impair the host's ability to control tuberculosis.
By studying the immune response to filarial worms, our lab hopes to develop novel methods to prevent and treat these infections.
We conduct studies in basic parasitology to increase our knowledge of filaria biology, enhance our ability to work with these organisms, and gain insights into novel anti-filarial drug and vaccine discovery. Studies in this area include proteomic analyses of different anatomical structures of filariae, development of model systems of filariasis, enhancement of in vitro cultivation of filarial worms, and identification of the nutritional requirements of filariae.
Protection against Allergy and Autoimmunity
In addition to conducting research on filarial diseases, we also study the beneficial effects of parasitic worms on allergy and autoimmunity. By increasing our understanding of how worms protect against these inflammatory conditions, we hope to develop insights into novel approaches to treat these diseases. Diseases studied in the lab include type 1 diabetes, lupus, immediate cutaneous hypersensitivity, and immune complex-mediated (Type III) hypersensitivity. Recently, we demonstrated that worms induce protection against type 1 diabetes by increasing host production of IL-10, a downregulatory cytokine. We have also shown in both mouse models and humans that chronic helminth infections make it more difficult to fully activate basophils, which are important allergy-effector cells, through their IgE receptors. Finally, we actively work to develop new therapies for allergic and autoimmune diseases by identifying mechanisms to replicate the immune responses induced by worms without using live parasites.
Ongoing research projects
- Establishing a small mammal model of lymphatic filariasis
- Development of an in vitro culture system for filarial worms
- Determining protective mechanisms of immunity against filarial infections
- Elucidating the immunologic mechanisms responsible for immunoregulation in helminth infections and allergy immunotherapy
- Elucidating the mechanisms by which nematodes protect against autoimmune diseases and allergy
- Developing novel, helminth-derived therapies for allergy and autoimmune diseases