ResearchMy primary interests involve immune regulation and response in the gastrointestinal tract where the body is in continuous contact with commensal and pathogenic bacteria. Helicobacter pylori (H. pylori) infection of the stomach provides an excellent model to study the host-pathogen relationship at mucosal surfaces since there are no competing bacteria to colonize and influence the host immune response.
Our research focuses on two different aspects of the anti-H. pylori immune response. The first explores the inability of the host to generate a protective immune response to H. pylori. Although immunization confers the ability to eradicate the infection in animal models, in the absence of immunization infection lasts for the life of the host. Our data suggest that activation of T cells at the gastric mucosa in response to infection results in the development of either down-regulatory or anergic T cells. These T cells fail to provide the help signals that are necessary to amplify the inflammatory response sufficiently to eradicate H. pylori. These T cells, similar to regulatory T cells in other tissues, are induced in a CTLA-4 dependent manner during antigen presentation. We are now studying why activation of T cells in the gastric lamina propria favors the development of T cells with this nonprotective phenotype.
We are also investigating the protective immune response that eradicates H. pylori from the gastric mucosa in immunized mice. These T cells are recruited to the gastric mucosa upon challenge with H. pylori and the response is dominated by Th-17 cells. IL-17 from these cells activates nonhematopoetic cells such as fibroblasts and epithelial cells to secrete chemokines that recruit and activate neutrophils. We are now studying why immunization favors the development of Th-17 cells and how the amplified inflammatory response actually kills H. pylori residing in the gastric lumen.
In addition to our studies on adaptive immunity, we also investigate H. pylori virulence factors through the generation of genetic deletions in clinical isolates of H. pylori. The importance of specific factors can then be evaluated by measuring growth kinetics, intracellular survival in phagocytes in vitro, and the ability to colonize animal models or induce gastric inflammation in vivo. Thus H. pylori can be used to study gastrointestinal immunity and microbial virulence.
Figure 1. During infection, bacterial antigens from the lumen are presented to naive T cells in the lamina propria resulting in a nonprotective response characterized by IFNy, Treg cel |
Lab Techniques
- Cell Culture (Lymphocytes, macrophages, dendritic cells, epithelial cells, fibroblasts, hybbridomas)
- Molecular Biology (Polymerase Chain Reaction, cloning)
- Immunochemistry (ELISA, Western Blotting, Immunohistochemistry, Flow Cytometry, Affinity Purification)
- Cell Assays (Proliferation, phagocytosis evaluation, activation markers, cytokine production, reactive oxygen species generation, antigen presentation)
- Microbiology (Helicobacter pylori, Probiotics strains, Gut commensals, Opportunistic pathogens)
Publications
- Anderson K, Czinn SJ, Redline RW, and Blanchard TG (2006). Induction of CTLA-4 mediated anergy contributes to persistent colonization in the murine model of gastric H. pylori infection. Journal of Immunology, 176, 5306-5313.
- Drakes ML, Czinn SJ, and Blanchard TG (2006). Regulation of murine dendritic cell immune responses by Helicobacter felis antigen. Infection and Immunity, 74, 4624-4633.
- Drakes ML, Blanchard TG, and Czinn SJ (2005). Colon lamina propria dendritic cells induce a proinflammatory cytokine response in lamina propria T cells in the SCID mouse model of colitis. Journal of Leukocyte Biology, 78, 1291-1300.
- Matsumoto Y, Blanchard TG, Drakes ML, Basu M, Redline RW, Levine AD, and Czinn SJ (2005). Eradication of Helicobacter pylori and resolution of gastritis in the gastric mucosa of IL-10 deficient mice. Helicobacter, 10, 407-415.
- Rahn W, Redline RW, and Blanchard TG (2004). Molecular analysis of Helicobacter pylori-associated gastric inflammation in chronically infected and immune mice. Vaccine, 23, 807-818.
- Basu M, Czinn SJ, and Blanchard TG (2004). Absence of catalase reduces long-term survival of Helicobacter pylori in macrophage phagosomes. Helicobacter, 9, 211-216.
- Drakes ML, Czinn SJ, and Blanchard TG (2004). Isolation and purification of colonic lamina propria dendritic cells. Cytotechnology, 151-161.
- Drakes M, Blanchard T, and Czinn S (2004). Enhanced cytokine release by probiotic-stimulated dendritic cells. Infection and Immunity, 72, 3299-3309.
- Busiello I, Acquaviva R, Di Popolo A, Blanchard TG, Ricci V, Romano M, and Zarrilli R (2004). Helicobacter pylori g-glutamyltranspeptidase upregulates COX-2 and EGF-related peptide expression in human gastric cells. Cellular Microbiology, 6, 255-267.
- Blanchard TG, Eisenberg JC, and Matsumoto Y (2004). Clearance of Helicobacter pylori infection through immunization: The site of T cell activation contributes to vaccine efficacy. Vaccine, 22, 888-97.
- Blanchard TG, Yu F, Hsieh C-L, and Redline RW (2003). Lack of phagocyte oxidase activity results in severe inflammation and a reduced bacterial load in murine Helicobacter pylori and felis infection. Journal of Infectious Diseases, 187, 1609-15.
- Eisenberg JC, Czinn SJ, Garhart CA, Redline RW, Bartolomae WC, Gottwein JM, Nedrud JG, Emancipator SE, Boehm BB, Lehmann PV, and Blanchard TG (2003). Protective anti-Helicobacter pylori immunity following systemic immunization of neonatal mice. Infection and Immunity, 71, 1820-7.
- McGovern KJ, Blanchard TG, Gutierrez JA, Czinn S, Krakowka S, and Youngman P (2001). Gamma-glutamyl transpeptidase is a Helicobacter pylori virulence factor but is not essential for colonization. Infection and Immunity, 69, 4168-4173.
- Gottwein JM, Blanchard TG, Targoni OS, Eisenberg J, Zagorski BM, Trezza RP, Redline RW, Nedrud JG, Tary-Lehmann M, Lehmann PV, and Czinn SJ (2001). Systemic vaccination with aluminum hydroxide induces protective immunity against Helicobacter pylori infection in mice. Journal of Infectious Disease, 184, 308-314.
- Robinson JK, Blanchard TG, Levine AD, Emancipator SN, and Lamm ME (2001). A mucosal IgA-mediated excretory immune system functions in vivo. Journal of Immunology, 166, 3688-3692.
Personal HistoryI obtained my PhD degree at the University of Massachusetts, Amherst in 1991 and subsequently joined a mucosal immunology research group in the Department of Pathology at the Case Western Reserve University School of Medicine as a post-doctoral fellow until 1997. During this period I also spent a semester as a Visiting Assistant Professor at Oberlin College where I taught the Immunology course and laboratory. In 1997 I joined the faculty of the CWRU Pathology Department and then in 1999 moved to the Pediatrics Department. I joined the University of Maryland School of Medicine in early 2007 with appointments in both Pediatrics and Microbiology. I am a member of several professional societies including the American Association of Immunologists, the American Society for Microbiology, the Society for Mucosal Immunology, and the American Gastroenterological Association. I review manuscripts for many journals including The Journal of Immunology, Gastroenterology, The Journal of Infectious Diseases, and Infection and Immunity. My research is supported by the National Institutes of Health. Laboratory PersonnelBack to All Faculty |
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