The long term objective is to determine the immunologic mechanisms in the pathogenesis of infection by the lymphatic-dwelling filariae. These infections, medically important in many tropical and subtropical areas, produce a range of clinical manifestations considered to be immunologically mediated but the immunologic mechanisms are not completely known. More detailed knowledge of the immunopathology would be of potential value for designing treatment regimes and development of immunization procedures. The proposed study will investigate the immunopathology of two manifestations of infection: tropical filarial eosinophilia (occult filariasis) and chronic lymphedema. The ferret (Mustela putorius furo) infected with Brugia malayi will be used as an experimental model.
Four specific aims are proposed. (1) To characterize the cellular responses to microfilariae in the liver resulting in the lesions of tropical eosinophilia and to identify the immune responses associated with development of these lesions. (2) By passive transfer of sera and measurement of antibody activity in the sera, to identify antibody responses which promote or inhibit the inflammatory reactions typical of tropical eosinophilia and to correlate these observations with in vitro studies of opsonic, cytophilic and blocking activity of the sera in leukocyte adherence and cytotoxicity tests with microfilariae. (3) To identify cytokines regulating eosinophil activity in infected ferrets by assays for chemotaxis/chemokinesis and by activation of adherence and cytotoxicity to microfilariae. (4) To examine the immune responses and the lymphatic pathology associated with the development of chronic edema in ferrets repeatedly infected with Brugia malayi.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI019275-05
Application #
3444619
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1983-03-01
Project End
1990-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
5
Fiscal Year
1988
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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