Judith A. Appleton, Ph.D.
Baker Institute for Animal Health
Alfred H. Caspary Professor of Immunology
As long as there have been animals, there have also been parasites. During her time as an active researcher at the Institute, Dr. Judy Appleton’s research focused on exploring parasitic diseases of animals, including the ways in which the body fights (or fails to fight) infection with the worm Trichinella spiralis; the immune response to the “brainworm”, Parelaphostrongylus tenuis; and ways to turn a parasite’s own chemical signals against itself. Dr. Appleton now serves as Vice Provost for the university.
The immune response to T. spiralis has been a special focus of Dr Appleton’s work. Long recognized as the foodborne cause of trichinelloosis, T. spiralis is found in pigs, rodents, and other animals. Trichinellosis infection rates are waning in developed countries, but it remains common in impoverished communities and in places where uncooked meat or home-smoked sausages are consumed. For many years, scientists who studied T. spiralis thought that the body defended itself by sending an army of eosinophils (white blood cells) to an infection site to fend it off. However, by using a strain of mice that lack eosinophils, Dr. Appleton and her colleagues showed that this is not always the case and that eosinophils actually help the parasite in certain ways. At the beginning of an infection, eosinophils prevent an animal’s own tissues from producing toxic nitric oxide that would otherwise kill off the parasite. They also help the parasite to grow by another mechanism that has yet to be elucidated. The discovery that eosinophils don’t always defend the body against T. spiralis has prompted researchers to reexamine their assumptions about interactions between eosinophils and other types of parasites, and it could lead to more effective treatments for T. spiralis infections.
Another worm under the lens in the Appleton lab, P. tenuis, has a complicated life cycle and poses a difficult problem for farmers in the Eastern half of the U.S. The worm is carried by white-tailed deer that shed the larvae in the environment where they may be picked up by terrestrial snails. Inside the snail, larvae develop into their infectious form, then leave the snail and cling to vegetation where they can be picked up by horses, cattle, sheep, alpacas, or llamas. The spread of the worm from deer makes the parasite very difficult to control in a farm setting, so livestock farmers are seeking a vaccine that can protect herds from infection. However, it’s unknown what sort of immune reaction these livestock species can mount naturally against the worm, making it difficult or impossible to design a vaccine to augment that response. Dr. Appleton’s lab investigated immune responses in alpacas and in sheep in order to determine whether being infected with the parasite once offers immune protection if an animal encounters the parasite again in the future. If so, vaccines might well offer some promise for controlling this difficult parasite.
Vaccines were also a goal in Dr. Appleton’s work with chemoattractants, chemicals that parasites employ to attract one another and find a mate. Infections with whipworm, Trichuris, a parasite that infects an estimated 604-795 million people worldwide, are currently treated with antiparasitic drugs, but resistance to these medications is a growing and serious problem. A vaccine that targets the machinery necessary for reproduction could help protect people and animals from these infections and avoid the risk of resistance, so Dr. Appleton and her colleagues, including Dr. Frank Schroeder at the Boyce Thompson Institute for Plant Research, collaborated to identify the small molecule chemoattractants that females of these species use to attract males. In the early stages of the work, they studied the closely related and more tractable T. spiralis as a stand-in for Trichuris. Their work identified two chemoattractant ascarosides (glycolipids that contain the sugar ascarylose). Suitable chemoattractants or conjugates of chemoattractants could eventually be used to formulate a vaccine or drug that would recognize whipworm infections and fight them off.
Links and abstracts for all of Dr. Appleton’s publications can be found at PubMed.
- Huang, L; Appleton, JA; (2016). Eosinophils in Helminth Infection: Defenders and Dupes. Trends in Parasitology, 32,(10), 798-807.
- Huang, L; Gebreselassie, NG; Gagliardo, LF; Ruyechan, MC; Luber, KL; Lee, NA; Lee, JJ; Appleton, JA; (2015). Eosinophils Mediate Protective Immunity against Secondary Nematode Infection. Journal of Immunology, Jan 1; 194(1):283-90.
- Huang, L; Beiting, DP; Gebreselassie, NG; Gagliardo, LF; Ruyechan, MC; Lee, NA; Lee, JJ; Appleton, JA; (2015) Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury. PLOS Pathogens, Dec 31; 11(12): e1005347.
- Huang, L; Gebreselassie, NG; Gagliardo, LF; Ruyechan, MC; Lee, NA; Lee, JJ; Appleton, JA; (2014). Eosinophil-Derived IL-10 Supports Chronic Nematode Infection. Journal of Immunology, Oct 15; 193(8): 4178-87.
- Jacobsen, EA; LeSuer, WE; Willetts, L; Zellner, KR; Mazzolini, K; Antonios, N; Beck, B; Protheroe, C; Ochkur, SI; Colbert, D; Lacy, P; Moqbel, R; Appleton, JA; Lee, NA; Lee, JJ; (2014). Eosinophil activities modulate the immune/inflammatory character of allergic respiratory responses in mice. Allergy, Mar; 69(3):315-27.
- Blum, LK; Mohanan, S; Fabre, MV; Yafawi, RE; Appleton, JA; (2013). Intestinal infection with Trichinella spiralis induces distinct, regional immune responses. Veterinary Parasitology, May 20; 194(2-4):101-5.
- Scalfone, LK; Nel, HJ; Gagliardo, LF; Cameron, JL; Al-Shokri, S; Leifer, CA; Fallon, PG; Appleton, JA; (2013). Participation of MyD88 and Interleukin-33 as Innate Drivers of Th2 Immunity to Trichinella spiralis. Infection and Immunity, Apr; 81(4):1354-63.
- Thrasher, SM; Scalfone, LK; Holowka, D; Appleton, JA; (2013). In vitro modelling of rat mucosal mast cell function in Trichinella spiralis infection. Parasite Immunology, Jan; 35(1):21-31.
- Appleton, JA; (2012). Costs and Benefits of Immunity to Worm Infection. Journal of Immunology, Aug 1; 189(3):1101-3.
- Purdy, SR; Gagliardo, LF; Lefman, S; Hamel, PJS; Ku, S; Mainini, T; Hoyt, G; Justus, K; Daley-Bauer, LP; Duffy, MS; Appleton, JA; (2012). Jul; 19(7):1019-26. Analysis of Heavy-Chain Antibody Responses and Resistance to Parelaphostrongylus tenuis in Experimentally Infected Alpacas. Clinical and Vaccine Immunology.
- Pinn, T; Stokol, T; Gagliardo, LF; Purdy, SR; Appleton, JA; (2012). Comparison of three immunoglobulin G assays for the diagnosis of failure of passive transfer of immunity in neonatal alpacas. Journal of Veterinary Internal Medicine. Jan; 25(1):91-8. Abstract.
- Gebreselassie, NG; Moorhead, AR; Fabre, V; Gagliardo, LF; Lee, NA; Lee, JJ; Appleton, JA; (2012). Eosinophils Preserve Parasitic Nematode Larvae by Regulating Local Immunity. Journal of Immunology, Jan 1; 188(1):417-25. Abstract.
- Mitreva, M; Jasmer, DP; Zarlenga, DS; Wang, ZY; Abubucker, S; Martin, J; Taylor, CM; Yin, Y; Fulton, L; Minx, P; Yang, SP; Warren, WC; Fulton, RS; Bhonagiri, V; Zhang, X; Hallsworth-Pepin, K; Clifton, SW; McCarter, JP; Appleton, JA; Mardis, ER; Wilson, RK; (2011). The draft genome of the parasitic nematode Trichinella spiralis. Nature Genetics, Mar; 43(3):228-35.
- Daley-Bauer, LP; Purdy, SR; Smith, MC; Gagliardo, LF; Davis, WC; Appleton, JA; (2010). Contributions of Conventional and Heavy-Chain IgG to Immunity in Fetal, Neonatal, and Adult Alpacas. Clinical and Vaccine Immunology, Dec; 17(12):2007-15.
- Jayaram, J; Papoyan, A; Bisharyan, Y; Cassidy-Hanley, D; Zhang, XJ; Colussi, P; Appleton, JA; Gagliardo, L; Clark, TG; (2010). An Alternative Platform for Rapid Production of Effective Subunit Vaccines. Biopharm International.