Center for Reproductive Biology

Participating Faculty


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Name: William Davis
Department: Veterinary Microbiology & Pathology
Credentials: 1967~Ph.D., Stanford University - Medical Microbiology, Transplantation Immunology
Office: Bustad 329
Phone: 509-335-6051
Fax: 509-335-8328
Mailing Address: Veterinary Microbiology &Pathology
PO Box 647040
Pullman, WA 99164-7040
E-mail: davisw@wsu.edu
Web Site: Click here

Research Interests

The study of mechanisms regulating the immune response to
infectious agents and vaccines.

Research Summary

The long term objectives of our research program are to elucidate the mechanisms regulating the immune response to infectious agents and develop protective vaccines. To achieve these objectives, we continue to develop and use monoclonal antibodies and assays to study the immune response in domestic animals with a primary focus on ruminants. M. avium subsp. paratuberculosis (Map) has been selected as the model pathogen for our investigations because of its economic importance and its potential for providing insight into the mechanisms regulating the immune response to Map and other intracellular pathogens. Map is the causative agent of Johne’s disease (JD) in cattle, a chronic wasting disease of the intestine. It causes significant economic loss to producers, especially the dairy industry, due to increase in forage consumption, decreased milk production and early culling due to poor health of affected animals. There is also a concern that Map is a zoonotic pathogen.  Map has been isolated from human patients with Crohn’s disease (CD), a chronic inflammatory disease of the intestine.  It is not clear whether Map is the etiologic agent causing Crohn’s disease.  However, recent studies on CD and mycobacterial pathogens M. tuberculosis (Mtb) and Map have shown a similarity in the mechanisms of pathogenesis at the cellular and molecular level.  The studies have revealed the cross regulation of the immune system by regulatory T cells and effector T cells mediating protective immune responses is dysregulated, giving rise to an imbalance that results in chronic inflammation of target tissues, and in the case of Mtb and Map dysregulation of protective immunity.  To extend these observations we developed a bovine cannulated ileum model to conduct studies on the mechanisms of pathogenesis mediated by Map in the natural host, studies that cannot be conducted in humans.  The model offers an opportunity study the interaction Map during the early and late stages of infection.  We have also developed a flow cytometric assay to analyze the immune response to Map and methods to elucidate the functional changes associated with dysregulation of the immune system.  We believe the studies will show Map could be involved in the pathogenesis of CD.  

The working hypothesis is:
Antigen presenting dendritic cells (DC) play a central role in the development and maintenance of protective immunity against Map and that dysregulation of DC function allows for disease progression.
 
The specific objectives to test the hypothesis are:
1) Determine how Map affects DC maturation and secretion of regulatory cytokines and chemokines in vitro.
2) Detail the primary CD4 and CD8 T cell immune responses mediated by immature DC (iDC) and matured DC (mDC) following exposure to different antigenic stimuli in vitro.
3) Determine if regulatory DC (DCr) and regulatory T cells (Tr) play a role in modulating the immune response to Map.

 

Research Publications

 Selected 2005-2009 

Seo KS, Davis WC, Hamilton MJ, Park YH, Bohach GA.  Development of monoclonal antibodies to detect bovine FOXP3 in PBMCs exposed to a staphylococcal superantigen.  Vet Immunol Immunopathol 128: 30-36, 2009.

Seo KS, Park JY, Davis WC, Fox LK, McGuire MA, Park,YH, Bohach GA.  Superantigen-mediated differentiation of bovine monocytes unto dendritic cells. J Leukoc Biol  85: 606-616, 2009.

Pargass, I.S., T.B. Wills, W.C. Davis, K.J. Wardrop, D.C. Alperin, and S.A. Hines, The influence of age and Rhodococcus equi infection on CD1 expression by equine antigen presenting cells. Vet Immunol Immunopathol, 2009. 130(3-4): p. 197-209.

Allen, A.J., K.T. Park, G.M. Barrington, K.K. Lahmers, M.J. Hamilton, and W.C. Davis, Development of a bovine ileal cannulation model to study the immune response and mechanisms of pathogenesis of paratuberculosis. Clin Vaccine Immunol, 2009. 16(4): p. 453-63.

Dassanayake, R.P., W. Liu, W.C. Davis, W.J. Foreyt, and S. Srikumaran, Bighorn sheep beta2-integrin LFA-1 serves as a receptor for Mannheimia haemolytica leukotoxin. J Wildl Dis, 2008. 44(3): p. 743-7.

Whelan C, Shuralev E, O’Keeffe G, Hyland P, Kwok HF,Snoddy P, O’Brien A, Connolly M, Quinn P, Groll M, Watterson T, Call S, Kenny K, Duignan A, Hamilton MJ, Buddle BM, Johnston JA, Davis WC, Olwill S, Clarke J.  Multiplex immunoassay for the serological diagnosis of Mycobacterium bovis infected cattle.  Clin Vaccine Immunol 15:1834-1838, 2008

Davis, W.C. and M.J. Hamilton, Use of flow cytometry to develop and characterize a set of monoclonal antibodies specific for rabbit leukocyte differentiation molecules. J Vet Sci, 2008. 9(1): p. 51-66.

Johnson, W.C., R.G. Bastos, W.C. Davis, and W.L. Goff, Bovine WC1(-) gammadeltaT cells incubated with IL-15 express the natural cytotoxicity receptor CD335 (NKp46) and produce IFN-gamma in response to exogenous IL-12 and IL-18. Dev Comp Immunol, 2008. 32(8): p. 1002-10.

Mealey, R.H., M.H. Littke, S.R. Leib, W.C. Davis, and T.C. McGuire, Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy. Vet Immunol Immunopathol, 2008. 121(1-2): p. 8-22.

Park, K.T., J.L. Dahl, J.P. Bannantine, R.G. Barletta, J. Ahn, A.J. Allen, M.J. Hamilton, and W.C. Davis, Demonstration of allelic exchange in the slow-growing bacterium Mycobacterium avium subsp. paratuberculosis, and generation of mutants with deletions at the pknG, relA, and lsr2 loci. Appl Environ Microbiol, 2008. 74(6): p. 1687-95.

Davis MS, Davis WC, Ensign WY, Hinchcliff KW, Holbrook TC, Williamson KK.  Effects of training and strenuous exercise on hematologic values and peripheral blood leukocyte subsets in racing sled dogs.  J Am Vet Med Assoc 232: 873-878, 2008.

Steinberg, J.D., C.S. Olver, W.C. Davis, J. Arzt, J. Johnson, and R. Callan, Acute myeloid leukemia with multilineage dysplasia in an alpaca. Vet Clin Pathol, 2008. 37(3): p. 289-97.

Dassanayake, R.P., S. Shanthalingam, W.C. Davis, and S. Srikumaran, Mannheimia haemolytica leukotoxin-induced cytolysis of ovine (Ovis aries) leukocytes is mediated by CD18, the beta subunit of beta2-integrins. Microb Pathog, 2007. 42(5-6): p. 167-73.
 


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