Amphibians (frogs, toads, and salamanders) are an essential part of many aquatic and terrestrial ecosystems. They consume algae and plants as tadpoles, consume many insects as adults, and become food for other animals such as birds and mammals. Currently, amphibians are declining around the world due to a new skin fungus. This project will investigate the immune responses of amphibians against this skin fungus using state-of-the art molecular and cellular assays. Whether amphibians can develop antibody responses or other immune cell-mediated responses will be determined. The project will evaluate immune responses in species that have high and low resistance to the fungus. Efforts will be made to develop an immunization protocol (vaccination strategy) to protect endangered amphibians in captivity. It is expected that amphibians can be induced to develop an immune response that may protect them from natural infection in the wild. This may allow for the reintroduction of endangered species that are currently held in captivity in zoos and aquariums. The project will provide training for students at the undergraduate and graduate school levels. It has the potential to expand our understanding of amphibian immunity in general. The overall project will enhance ongoing partnerships with an international group of scientists addressing the problem of global amphibian declines and support amphibian conservation efforts.
Intellectual Merit: The chytrid fungus, Batrachochytrium dendrobatidis (Bd), has been linked to global amphibian population declines. Although amphibians possess robust immune defenses, many species are highly susceptible to this pathogen. Because frogs are useful models for studies of immunity, we have employed them to investigate the interactions between this fungal pathogen and its amphibian hosts. Over the course of these studies we have demonstrated that lymphocytes and antibodies are involved in immune responses against this pathogen. However, these responses are modest and somewhat ineffective. Therefore, we investigated the hypothesis that these relatively weak immune responses may be because this fungus has evolved mechanisms to evade host immune defenses. We have shown that the fungus produces factors that inhibit lymphocyte proliferation and induce the death of lymphocytes that come into contact with the fungal products. In ongoing experiments, we have also shown that the factors produced by the amphibian chytrid fungus (B. dendrobatidis) can inhibit lymphocyte functions of humans and mice. This suggests that the factors target fundamental processes shared by amphibians and mammals and could be potentially useful for the treatment of human autoimmune diseases such as lupus erythematosus or multiple sclerosis. Alternatively, they might be useful for eventual treatment of lymphoid cancers. In future studies, we plan to isolate and further characterize the molecules that alter lymphocyte functions. Broader Impacts: The project has served to train a high school student and a number of undergraduate and graduate students. The discovery of the production of lymphocyte inhibitory factors by this primitive fungus suggests future studies to identify and characterize the active molecules and determine whether they could be used for treatment of human diseases.
