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Faculty Stephen K. Wikel
Professor of Cell Biology and Immunology
swikel@up.uchc.edu
Read about Dr. Wikel's research in the Summer 2006 issue of
UConn
Health Center Magazine
Areas of Interest:
Emerging and re-emerging tick transmitted diseases are significant
global public health problems. The focus of the research in this
laboratory is the characterization of the complex cellular and molecular
immunology of the tick-host-pathogen interface. During the course of
blood feeding, ticks introduce pharmacologically active molecules into
the host that are essential for obtaining a blood meal and for
successful transmission of disease-causing agents. Many of these
molecules stimulate host immune responses that induce resistance to tick
feeding. In turn, ticks have developed immunomodulatory countermeasures,
which suppress or deviate host innate and acquired immunity.
Interactions between host immunity and tick mediated immunomodulation
are central to successful tick feeding and pathogen transmission.
Immunomodulatory proteins in tick saliva are being isolated and
characterized, and the genes encoding those molecules are being cloned
and expressed.
In addition to immunomodulatory molecules, tick salivary glands
produce a plethora of pharmacologically active molecules that include
vasodilators as well as inhibitors of the coagulation pathways, platelet
aggregation, and irritation at the bite site. An expressed sequence tags
(ESTs) project is in progress to identify genes encoding anti-hemostasis,
immunomodulatory and other factors, expressed in the salivary glands of
the feeding tick, that contribute to successful feeding and pathogen
transmission. The EST approach is combined with a proteomics approach to
discovering important tick salivary gland proteins.
In addition to providing new insights into tick-host-pathogen
interactions, a goal of this research is to develop a novel
"vector-blocking" vaccine, which will target those molecules introduced
by the tick that are essential for feeding and pathogen transmission.
This strategy will circumvent the need to develop vaccines for each
individual tick-borne pathogen.
Collaborations are maintained with the other members of the Center
for Microbial Pathogenesis and with scientists at the Centers for
Disease Control and Prevention, the University of Texas Southwestern
Medical Center, and the National Institutes of Health.
Lab Rotation Projects:
Mosquito saliva contains pharmacologically active molecules that are
essential for successful blood feeding and transmission of infectious
agents. Recent studies have found that mosquito feeding results in
changes in the predominant cytokine secretion profiles of antigen or
mitogen stimulated T-lymphocytes from infested mice. Theses changes
persist for days after the mosquito bite. All studies reported to date
involved analysis of batch cultures stimulated in vitro.
Proposed rotation project will involve characterization of ex vivo
intracellular cytokine responses of CD4+ and CD8+ T-lymphocytes at
selected times after feeding of either 10 or 25 Aedes aegypti on a C3H/HeN
mouse. Pooled axillary and brachial lymph nodes and splenocytes from
mosquito exposed and control mice will be stimulated in vitro with PMA
and ionomycin. Cell proliferation will be assessed by CFSE dilution.
Publications
Selected Publications:
Wikel, S.K., Alarcon-Chaidez, F. and Müller-Doblies, U. 2004.
Immunological control of blood feeding arthropods. In, Biology of
Disease Vectors. Second edition. J. Hemingway, editor. Academic Press,
San Diego (Invited chapter in press).
Brossard, M. and Wikel, S.K. 2004. Tick immunobiology. Parasitology
(In press).
Boppana, D.K.V., Raj, D., John, L., Wikel, S.K., Latha, B.R. and
Gomathinayagam, S. 2004. In vivo immunomodulatory effects of
ixodid ticks on ovine circulating T and B-lymphocytes. Parasite
Immunology (In press).
Alarcon-Chaidez, F.J., Müller-Doblies, U. and Wikel, S.K. 2003.
Characterization of a recombinant immunomodulatory protein from the
salivary glands of Dermacentor andersoni. Parasite Immunology
25:69-77.
Anderson, J.F., Main, A.J., Andreadis, T.G., Wikel, S.K. and
Vossbrinck, C.R. 2003. Transstadial transmission of West Nile virus by
three species of ixodid ticks (Acari: Ixodidae). Journal of Medical
Entomology 40:528-533.
Clawson, M.L., Paciorkowski, N., Rajan, T.V., La Vake, C., Pope, C.,
La Vake, M., Wikel, S.K., Krause, P.J., and Radolf, J.D. 2002. Cellular
immunity, but not IFN-γ, is essential for resolution of Babesia
microti infection in BALB/c mice. Infection and Immunity
70:5304-5306.
Wikel, S.K. and Alarcon-Chaidez, F.J. 2001. Progress toward
characterization of the molecular basis for arthropod modulation of host
immunity. Veterinary Parasitology 101:275-287.
Macaluso, K.R. and Wikel, S.K. 2001. Dermacentor andersoni:
effects of repeated infestations on lymphocyte proliferation, cytokine
production, and adhesion molecule expression by BALB/c mice. Annals of
Tropical Medicine and Parasitology 95:413-427.
Schoeler, G.B. and Wikel, S.K. 2001. Modulation of host immunity by
hematophagous arthropods. Annals of Tropical Medicine and Parasitology
95: 755-771.
Schoeler, G.B., Manweiler, S.A., Bergman, D.K. and Wikel, S.K. 2000.
Influence of repeated infestations with pathogen-free Ixodes scapularis
(Acari: Ixodidae) on in vitro lymphocyte proliferative responses
of C3H/HeN mice. Journal of Medical Entomology 37:885-892.
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