Performing Department
Molecular Biology
Non Technical Summary
The parasite Toxoplasma gondii (T. gondii) is the third leading cause of food borne illness in the U.S. Infection rates range between 30-70% in many animal species, including livestock, and as such is a major food safety issue world wide. In humans, there are over 1,075,242 primary infections per year caused mostly by ingestion of contaminated meat products with annual cost of illness of 3 billion dollars. In addition to the food safety threat, it is also one of the top reasons behind infectious abortion in livestock, especially sheep and goats resulting in significant losses in annual animal productivity. Infection of pigs, chickens, goats, sheep and cattle occurs when their food and water is contaminated by the excreted cat form of the parasite known as the oocyst. To date, no effective vaccines or drug treatments exist to completely protect against or clear T. gondii infection in livestock. In Europe, one attempt has been made to produce a safe and effective ovine vaccine against T. gondii. This treatment (Toxovax) was only partially effective and lasted for only 18 months. Therefore, development of a safe and effective vaccine for livestock is essential to improve animal health and livestock production while also improving food safety by reducing transmission to humans and thus, food-borne illness associated with this pathogen. Although a T cell population, known as the CD8 T cell, is widely recognized as a key player in long-term control of infection, a recent study using a new Toxoplasma vaccine strain identified a second important type of cell, the natural killer (NK) cell for immunity. NK cells are classically thought to be part of the early immune response, known as the innate immune response. They are effective against cancer and infectious disease and classically not thought to last a long time. This viewpoint has started to change. Recent studies suggest NK cells may become long-lived and be potent contributors to long-lasting immune responses, known as adaptive immune responses. This is important for vaccine development for livestock because if we can understand how to make them have memory to a pathogen, they would be useful in protecting against infection and increase the efficacy of the vaccine. A major obstacle in trying to stimulate NK cells to have memory is that the factors required to make them develop this trait are not well known. We now have found that NK cells are absolutely required for long-lasting immunity to Toxoplasma gondii infection. We do not understand how this occurs. The goal of this project is to define how they develop this response so we can better design vaccines to improve animal health, productivity and improve food safety.
Animal Health Component
100%
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
Currently, no vaccines or drugs are capable of adequately treating Toxoplasma in livestock. An effective vaccine for T. gondii in agricultural animals should accomplish two goals: 1) reduce infection induced abortions, and 2) Reduce or eliminate parasite tissue burdens in food animals to prevent food source contamination. Good vaccine design relies on a good knowledge base. To this end, our major goal is to increase knowledge of immune system function required for optimal immunity to Toxoplasma so we can design a highly effective vaccine or treatment to improve animal health. Specifically, we will dissect the role of Natural Killer cells (NK) in adaptive immunity to T. gondii and define mechanism(s) behind this functional development. To improve agriculture animal health and prevent infection induced abortions caused by the parasite Toxoplasma gondii. We will investigate how the Natural Killer cell plays a role in long lasting immune responses to this pathogen. We will then dissect the mechanisms by which they develop this activity. Achieving the goals will improve vaccine and therapy efficacy to treat this infection.
Project Methods
The methods for this project will include a mouse based model of infection with Toxoplasma gondii. We will also heavily use flow cytometry to characterize and determine what the Natural Killer cells are doing during different times of infection. We will use antibody treatments and transgenic animals to follow the fate of natural killer cells over time. All methodologies are standard immunology and cell biology techniques. Specific methods are included in the attached proposal.