Faculty with Emeritus Status      Back to Main

Faculty Detail    
Name LESLEY E SMYTHIES
 
Campus Address SHEL 606 Zip 2182
Phone  (20-5) -254
E-mail  lesmy@uab.edu
Other websites
     

Education
Undergraduate  King's College, London University    1976  B.S. in Biology 
Graduate  King's College, London University    1982  Ph.D. in Physiology 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Medicine  Med - Gastroenterology Professor Emeritus
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Emeritus

Biographical Sketch 
Dr. Smythies earned her B.Sc. (Hons), A.K.C. at Kings College, London University, England and her Ph.D. at Wye College, London University. She then did postdoctoral fellowships in the Department of Physiology and Biophysics at UAB and the Department of Biology at the University of York, England. She returned to UAB and joined the Department of Medicine as a Research Associate in 1998, advancing to Research Assistant Professor in 2002 and Associate Professor in 2006.

Society Memberships
Organization Name Position Held Org Link
British Cytokine Group     
British Lung Foundation and Thoracic Society     
British Society for Immunology     
British Society for Parasitology     
Society for Leukocyte Biology     
Society for Mucosal Immunology     



Research/Clinical Interest
Title
Immunobiology of human mucosal infections; stromal (fibroblast) regulation of antigen-presenting cells (intestinal macrophages and dendritic cells) in the gastric and intestinal mucosa.
Description
Dr. Smythiesí research focus is human mucosal immunology, in particular the immunobiology of mucosal antigen presenting cells (macrophages and dendritic cells), and the host immunological response to parasite and bacterial pathogens. She focused originally on pulmonary immunology, helping to define the T cell cytokine regulation of the host response to Schistosoma mansoni. She went on to elucidate the role of interferon-gamma regulation of nitric oxide production in host defense against African trypanosome infections. Recently, she turned her investigative attention to the mucosal immune response to Helicobacter pylori. Using a mouse model of the infection that she developed, she has shown that H. pylori inflammation is Th1-mediated and with colleagues is exploring the protective T regulatory cell response of children versus adults to infection with H. pylori. Recent studies in her laboratory have focused on intestinal extracellular (stromal) immune matrix regulation of primary human mucosal macrophages and dendritic cells in mucosal infections and in IBD. In highly novel studies, she has shown that the lamina propria stroma (including intestinal fibroblasts) plays a critical role in monocyte differentiation into non-inflammatory, but powerfully bactericidal, intestinal macrophages and she has elucidated the defective signal transduction pathway(s) underlying the down-regulated inflammatory response of intestinal macrophages to bacterial antigens. New studies elucidate how the lamina propria stroma also conditions intestinal dendritic cell and mucosal T cell function. Dr Smythies was also the first to identify, isolate and characterize human gastric dendritic cells and to show that the microenvironment of the gastric mucosa conditions and regulates gastric dendritic cell responses to H. pylori infection which, in turn, drive responsive CD4 T cell proliferation and IFN-gamma release against H. pylori.

Selected Publications 
Publication PUBMEDID
1. Smythies, L.E., Pemberton, R.M., Coulson, P.S., and Wilson, R.A. T cell-derived cytokines associated with pulmonary immune mechanisms in mice vaccinated with irradiated cercarie of Schistosomamansoni. J. Immunol. 148:1512-1518, 1992.  1538133 
2. Smythies, L.E., Coulson, P.S., and Wilson, R.A. Monoclonal antibody to IFN-gamma abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae. J. Immunol. 149: 3654-3658, 1992.  1431135 
3. Wilson, R.A., Coulson, P.S., Betts, C., Dowling, M-A., and Smythies, L.E. Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-gamma receptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology. 87: 275-282, 1996.  8698391 
4. Mabbott, N.A., Coulson, P.S., Smythies, L.E., Wilson, R.A., and Sternberg, J.M. African trypanosome infections that lack the interferon-gamma receptor gene: nitric oxide-dependent and –independent suppression of Tcell prolifative responses and the development of anaemia. Immunology. 94:476-480, 1998.  9767434 
5. Novak, M. J., Smythies, L.E., McPherson, S.A., Smith, P.D., and Morrow, C.D. Poliovirus replicons encoding the B subunit of Helicobacter pylori urease elicit a Th1 immune response. Vaccine. 17: 2384-2391, 1999.  10392620 
6. Smythies, L.E., Waites, K.B., Lindsey, J.R., Harris, P.R., Ghiara, P., and Smith, P.D. Helicobacter pylori–induced mucosal inflammation is Th1-mediated and exacerbated in interleukin-4, but not interferon-gamma, gene-deficient mice. J. Immunol. 165:1022-1029, 2000.  10878379 
7. Smythies, L.E., Chen, J-A., Lindsey, J.R., Ghiara, P., Smith, P.D., and Waites, K.B. Quantitative analysis of Helicobacter pylori infection in a mouse model. J. Immunol. Meth. 242:67-78, 2000.  10986390 
8. Smith, P.D., Smythies, L.E., Mostellar-Barnum, M., Sibley, D., Russell, M., Merger, M., Sellers, M. T., Orenstein, J. M., Shimada, T., Graham, M.F. and Kubagawa, H. Intestinal macrophages lack CD14 and CD89 and consequently are downregulated for LPS- and IgA-mediated activities. J. Immunol. 167: 2651-2656, 2001.  11509607 
9. L.E. Smythies, M.J. Novak, K.B. Waites, J.R. Lindsey, C.D. Morrow and P.D. Smith. Poliovirus replicons encoding the B subunit of Helicobacter pylori urease protect mice against H. pylori infection. Vaccine (2005) 23:901-909.  15603891 
10. Smythies, L.E., Sellers, M., Clements, R.H., Mosteller-Barnum, M., Meng, G., Benjamin, W.H., Orenstein, J.M. and Smith, P.D. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J. Clin. Invest. 115:66-75, 2005.  15630445 
11. L.E. Smythies, L. Wahl, S.M. Wahl and P.D. Smith. Isolation of monocytes and intestinal macrophages from human peripheral blood and tissue. Current Protocols in Immunology (2006) 7.6B.1-9.   
12. P.D. Smith, C. Ochsenbauer-Jambor and L.E. Smythies. Intestinal macrophages: unique effector cells of the innate immune system. Immunological Review (2006) 149-159.   
13. F. Leon, L.E. Smythies, P.D. Smith and B.L. Kelsall. Involvement of Dendritic Cells in the Pathogenesis of Inflammatory Bowel Disease. Advances in Experimental Medicine and Biology (2006) 579:117-132.  16620015 
14. P.R. Harris, S. Wright, C. Serrano, F. Riera, I. Duarte, J.Torres, A. Peña, A. Rollán, P. Viviani, E. Guiraldes, J. Schmitz, R.G. Lorenz, L. Novak, L.E. Smythies and P.D. Smith. Helicobacter pylori gastritis in children is associated with a T regulatory cell response. Gastroenterology (2008) 134:491-499.  18242215 
15. L.E. Smythies, R. Shen, D. Bimczok, L. Novak, R.H. Clements, E.R. Drelichman, D.E. Eckhoff, P. Bouchard, M.D. George, S. Dandekar and P.D. Smith. Inflammation anergy in human intestinal macrophages is due to Smad-induced IkappaBalpha; expression and NF-κB Inactivation. Journal of Biological Chemistry (2010) 285:19593-19604. PMCID: PMC2885238.  20388715 
16. D. Bimczok, R.H. Clements, K.B. Waites, L. Novak, D.E. Eckhoff, P.J. Mannon, P.D. Smith and L.E. Smythies. Human primary gastric dendritic cells induce a Th1 response to H. pylori. Mucosal Immunology (2010) 3:260-269. PMCID: PMC3683837.  20237463 
17. R. Shen, L.E. Smythies (Joint first authors), R.H. Clements, L. Novak and P.D. Smith. Dendritic cells transmit HIV-1 through human small intestinal mucosa. Journal of Leukocyte Biology (2010) 87:663-670. PMCID: PMC2858307.  20007245 
18. K.R. Huff, L.N. Akhtar, A.L. Fox, J.A. Cannon, P.D. Smith and L.E. Smythies. Extracellular matrix-associated cytokines regulate CD4+ effector T-cell responses in the human intestinal mucosa. Mucosal Immunology (2011) doi: 10.1038/mi.2010.86. PMCID: PMC3118864  21228771 
19. D. Bimczok, J.M. Grams, R.D. Stahl, K.B. Waites, L.E. Smythies, and P.D. Smith. Stromal Regulation of Human Gastric Dendritic Cells Restricts the Th1 Response to H. pylori. Gastroenterology (2011) 141:929-938. PMCID: PMC3163821.  21699795 
20. R. Shen, G. Meng, C. Ochsenbauer, P.R. Clapham, J. Grams, L. Novak, J.C. Kappes, L.E. Smythies and P.D. Smith. Stromal down-regulation of macrophage CD4/CCR5 expression and NF-κB activation mediates HIV-1 non-permissiveness in intestinal macrophages. PLoS Path (2011) 7:e1002060. doi: 10.1371 PMCID: PMC3102716.   21637819 
21. D. Bimczok, L.E. Smythies, K.B. Waites, J.M. Grams, R.D. Stahl, P.J. Mannon, S. Peter, C.M. Wilcox, P.R. Harris, S. Das, P.B. Ernst, and P.D. Smith. Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells. Journal of Immunology (2013) 12:6626-6634. PMCID: PMC3725581  23686492 
22. Harris PR, Smythies LE, Smith PD and Perez-Perez G. Role of childhood infection in the sequelae of H. pylori disease. Gut Microbes 2013 – In press.  24275060 

Keywords
Human. Fibroblasts, stroma (extracellular matrix) intestinal macrophages and dendritic cells, H. pylori, Crohn's disease.