This grant proposes to investigate the mechanisms by which ticks modulate host immunity during feeding and how the hosts can acquire increased resistance over repeated infections, resulting in decreased tick fitness. The PI and colleagues have identified an immunosuppressant protein, P36, which is produced in the salivary glands of the tick and secreted into the host wound site. Evidence supports this protein as having immunomodulatory properties. The long-term goal of this research is to understand the cellular and molecular bases by which ticks modulate host immune and to use tick derived immunomodulatory proteins as immunogens in a novel anti-tick vaccine.
Specific aims of this grant are: 1) express p36, using a baculovirus expression system, and determine the extent to which both the native and recombinant p36 proteins reduce Con A stimulated lymphocyte proliferation and modulate T-lymphocyte and macrophage cytokine levels in vitro. 2) Determine if immunization with p36 induces an immune response that impairs tick feeding. 3) Examine the temporal expression of p36 mRNA and protein throughout the life cycle and feeding cycle of D. andersoni and determine if p36 is present in the salivary glands of other medically important ixodid ticks. And 4) purify and clone additional immunomodulatory proteins from two size ranges previously identified using preparative SDS-PAGE fractionation, as well as determine their immunomodulatory activities and utility as vaccine immunogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI046676-02
Application #
6324475
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Aultman, Kathryn S
Project Start
2000-01-15
Project End
2003-12-31
Budget Start
2000-07-01
Budget End
2000-12-31
Support Year
2
Fiscal Year
2000
Total Cost
$162,645
Indirect Cost
Name
University of Connecticut
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Hill, Catherine A; Wikel, Stephen K (2005) The Ixodes scapularis Genome Project: an opportunity for advancing tick research. Trends Parasitol 21:151-3
Maxwell, S S; Stoklasek, T A; Dash, Y et al. (2005) Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells. Ann Trop Med Parasitol 99:661-72
Dash, Y; Maxwell, S S; Rajan, T V et al. (2005) Murine extramedullary erythropoiesis induced by tick infestation. Ann Trop Med Parasitol 99:518-31
Alarcon-Chaidez, Francisco J; Wikel, Stephen K (2004) Comparative aspects of the tick-host relationship: immunobiology, genomics and proteomics. Symp Soc Exp Biol :185-209; discussion 243-5
Brossard, M; Wikel, S K (2004) Tick immunobiology. Parasitology 129 Suppl:S161-76
Alarcon-Chaidez, Francisco J; Muller-Doblies, Uwe U; Wikel, Stephen (2003) Characterization of a recombinant immunomodulatory protein from the salivary glands of Dermacentor andersoni. Parasite Immunol 25:69-77
Schoeler, G B; Wikel, S K (2001) Modulation of host immunity by haematophagous arthropods. Ann Trop Med Parasitol 95:755-71
Wikel, S K; Alarcon-Chaidez, F J (2001) Progress toward molecular characterization of ectoparasite modulation of host immunity. Vet Parasitol 101:275-87
Bergman, D K; Palmer, M J; Caimano, M J et al. (2000) Isolation and molecular cloning of a secreted immunosuppressant protein from Dermacentor andersoni salivary gland. J Parasitol 86:516-25