Larvae of cestode parasites cause disease in man and domestic animals. In man the larvae of Taenia solium often invade the central nervous system and cause a disease known as neurocysticercosis which has numerous neurological complications including blindness, dementia, convulsions and, not infrequently, death. The infection is characterized by an inefficient and inconsistent cellular immune response but often an intense humoral immune response. It has been shown in several taeniid parasite-host relationships that immune responses are suppressed. In recent experiments we have demonstrated that larvae of Taenia crassiceps in BALB/c mice induce immunosuppression of Th1-like responses, which one would expect to be involved in anti-larval cellular responses; Th2 responses are relatively unaffected. It was also determined that these larvae secrete a glycoprotein of 175 Kd (gp175), consisting of peptide subunits of 68 and 55/52 kDa, which selectively downregulates Th1 responses. Earlier we described similar secreted molecules by larvae of T. solium in patients with neurocysticercosis but did not determine their biological effects. Recent experiments have shown that gpl75 suppresses the ability of human peripheral blood lymphocytes to respond to stimulation with phytohemagglutinin. In the present proposal we are requesting support to continue the studies on the biological role of gpl75 by determining its activities in downregulating both the induction and expression of immune responses, the effects of neutralizing gpl75 on growth and development of larvae in vivo, and to clone the genes and produce recombinant subunit peptides in order to more readily determine the immunoregulatory activity of this parasite- derived immunosuppressive molecule.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI035730-02
Application #
2390396
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1996-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Toenjes, S A; Kuhn, R E (2003) The initial immune response during experimental cysticercosis is of the mixed Th1/Th2 type. Parasitol Res 89:407-13
Spolski, R J; Alexander-Miller, M A; Kuhn, R E (2002) Suppressed cytotoxic T lymphocyte responses in experimental cysticercosis. Vet Parasitol 106:325-30
Spolski, R J; Thomas, P G; See, E J et al. (2002) Larval Taenia crassiceps secretes a protein with characteristics of murine interferon-gamma. Parasitol Res 88:431-8
Mooney, K A; Spolski, R J; See, E J et al. (2000) Immune destruction of larval taenia crassiceps in mice. Infect Immun 68:2393-401
Spolski, R J; Corson, J; Thomas, P G et al. (2000) Parasite-secreted products regulate the host response to larval Taenia crassiceps. Parasite Immunol 22:297-305
Toenjes, S A; Spolski, R J; Mooney, K A et al. (1999) The systemic immune response of BALB/c mice infected with larval Taenia crassiceps is a mixed Th1/Th2-type response. Parasitology 118 ( Pt 6):623-33
Toenjes, S A; Spolski, R J; Mooney, K A et al. (1999) gamma delta T cells do not play a major role in controlling infection in experimental cysticercosis. Parasitology 119 ( Pt 4):413-8