Wang, Xisheng, D.V.M., Ph.D.
D.V.M., China Agricultural University, Beijing, China, 1997
Ph.D., Immunology, Virginia Tech, Virginia, 2006
Immunomodulation of dendritic cell functions by Mycobacterium tuberculosis
- Evaluation of effects of ESAT-6 (early secreted antigenic target of 6 kD of M. tuberculosis) on dendritic cells
Understanding the mechanisms by which ESAT-6 modulates dendritic cell functions
Tuberculosis has caused disease in humans for thousands of years, and remains a major burden to human health, infecting more than one-third of the world’s population and causing almost two million deaths yearly worldwide. An effective vaccine is essential for global control of this disease. However its development is hampered by lack of information about the interactions between the bacterium that causes tuberculosis and human cells. ESAT-6 is a secreted M. tuberculosis protein that causes strong immune responses and is a candidate for inclusion in new antituberculosis vaccines. Dendritic cells are critical for presenting microbial antigens to lymphocytes and to generating effective immunity. We recently found that ESAT-6 modulates the function of human dendritic cells, making them more likely to stimulate pathologic inflammatory responses rather than protective immunity. We are working to understand the mechanisms through which ESAT-6 exerts these effects on dendritic cells. This information is critical to design more effective ESAT-6-based antituberculosis vaccines.
Selected papers and abstracts:
- Wang, X., H. Peng, P. F. Barnes, H. Tang, J. C. Townsend, B. Samten. 2011. The mycobacterium tuberculosis early secreted antigenic target of 6 kDa inhibits T cell interferon-gamma production through the p38 mitogen-activated protein kinase pathway. J. Biol. Chem. 286(27):24508-24518. First two authors equally contributed to the work.
- Feng, Y., Y. Kong, P. F. Barnes, F.F. Huang, P. Klucar, X. Wang, B. Samten, M. Sengupta, B. Machona, R. Donis, A. R. Tvinnereim, and H. Shams. 2011. Exposure to cigarette smoke inhibits the pulmonary T-cell response to influenza virus and Mycobacterium tuberculosis. Infect. Immun. 79: 229-237.
- Suzuki, Y., X. Wang, B. S Jortner, L. Payne, Y. Ni, S. A. Michie, B. Xu, T. Kudo, and S. Perkins. 2010. Removal of toxoplasma gondii cysts from the brain by perforin-mediated activity of CD8+ T Cells. Am. J. Pathol. 176:1607-1613.
- Wen, X., K. Tomoya, P. Laura, X. Wang, R. Laurel, and S. Yasuhiro. 2010. Predominant IFN-gamma-mediated expression of CXCL9, CXCL10, and CCL5 proteins in the brain during chronic Infection with toxoplasma gondii in BALB/c mice resistant to development of toxoplasmic encephalitis. J. Interferon Cytokine Res. 30(9):653-60.
- Wang, X., P. F. Barnes, K. M. Dobos-Elder, J. C. Townsend, Y. Chung, H. Shams, E. W. Stephen, and B. Samten. 2009. ESAT-6 inhibits production of IFN-gamma by Mycobacterium tuberculosis-responsive human T cells. J. Immunol. 182:3668-3677.
- Buka, S., X. Wang, and P. Barnes. 2009. Mycobacterium tuberculosis ESX-1 system-secreted protein ESAT-6 but not CFP10 inhibits human T-cell immune responses. Tuberculosis. 89 Suppl 1:S74-6.
- Wang, X. and Y. Suzuki. 2007. Microglia produce IFN-gamma independently from T cells during acute toxoplasmosis in the brain. J. Interferon Cytokine Res. 27:599-605.
- Wang, X., S. A. Michie, B. Xu, Y. Suzuki. 2007. Importance of IFN-gamma-mediated expression of endothelial VCAM-1 on recruitment of CD8+ T cells into the brain during chronic Infection with Toxoplasma gondii. J. Interferon Cytokine Res. 27:329-38.
- Suzuki, Y., S. Halonen, X. Wang, and X. Wen. 2007. Cerebral toxoplasmosis: Pathogenesis and host resistance, Pages 567-591, in Toxoplasma Gondii The Model Apicomplexan: Perspectives and Methods, Edited by Louis M. Weiss and Kami Kim, Elsevier Ltd (Book chapter).
- Miller, R., X. Wen, B.Dunford, X. Wang, and Y. Suzuki. 2006. Cytokine production of CD8+ immune T cells, but not of CD4+ T Cells, from Toxoplasma gondii-infected mice is polarized to a type-1 response following stimulation with tachyzoite-infected macrophages. J. Interferon Cytokine Res. 26:787-92.