It is proposed to use Brugia malayi (subperiodic strain) infection in the ferret, Mustela putorius furo as an experimental model for the study of immunobiology and pathology of lymphatic dwelling filariae. The study will elucidate the immunologic mechanisms responsible for occult infection by determining the antibody response promoting clearance of microfilariae, for inducing the characteristic inflammatory responses to microfilariae and the immunoregulating factors which may modulate the cellular responses to microfilariae typical of occult infections. A histologic and ultrastructural study will be done to determine the development and composition of the characteristic lesions of occult filariasis, the Meyers-Kouwenaar body. The ferret will be evaluated as an experimental host for the study of transient lymphatic disease and chronic obstructive disease following small repeated inoculations of infective larvae. The development and duration of lymphatic disease will be correlated with immunologic responses including changes in immediate and delayed hypersensitivity to parasite antigens. The proposed study is designed to identify mechanisms in immunopathogenesis in occult infections and lymphatic disease in filarial infection and should contribute to understanding the disease in man and have eventual application to treatment and prevention of human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI019275-03
Application #
3444618
Study Section
(SSS)
Project Start
1983-03-01
Project End
1986-11-30
Budget Start
1985-03-01
Budget End
1986-11-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Crandall, R; Crandall, C; Nayar, J et al. (1994) Resistance and disease in Brugia malayi infection of ferrets following prior infection, injection of attenuated infective larvae and injections of larval extracts. Parasite Immunol 16:425-33
Crandall, R; Crandall, C; Doyle, T et al. (1993) Immune responses and chronic lymphedema in experimental filariasis. Lymphology 26:120-7
Case, T C; Unger, E; Bernas, M J et al. (1992) Lymphatic imaging in experimental filariasis using magnetic resonance. Invest Radiol 27:293-7
Case, T; Leis, B; Witte, M et al. (1991) Vascular abnormalities in experimental and human lymphatic filariasis. Lymphology 24:174-83
Crandall, R B; Crandall, C A; Nayar, J K (1990) Injection of microfilariae induces resistance to Brugia malayi infection in ferrets and accelerates development of lymphostatic disease. Parasite Immunol 12:229-32
Hines, S A; Crandall, R B; Crandall, C A et al. (1989) Lymphatic filariasis. Brugia malayi infection in the ferret (Mustela putorius furo). Am J Pathol 134:1373-6
Witte, M; McNeill, G; Crandall, C et al. (1988) Whole body lymphangioscintigraphy in ferrets chronically infected with Brugia malayi. Lymphology 21:251-7
Thompson, J P; Crandall, R B; Doyle 4th, T J et al. (1987) Enhanced inflammation to Brugia malayi microfilariae in ferrets infected with Trichinella spiralis. J Parasitol 73:1274-6
Crandall, R B; Crandall, C A; Hines, S A et al. (1987) Peripheral lymphedema in ferrets infected with Brugia malayi. Am J Trop Med Hyg 37:138-42
Thompson, J P; Crandall, R B; Doyle 4th, T J et al. (1986) Antibody and cellular immune responses to microfilarial antigens in ferrets experimentally infected with Brugia malayi. Z Parasitenkd 72:525-35

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