Stephen J. McSorley, Ph.D. Associate Professor Department of Medicine Glasgow University, 1995, Ph.D. mcsor002@umn.edu 612-626-9905 office 612-626-9959 lab

Research Interests:

Immunity to Salmonella

Salmonella typhi causes typhoid fever, a common infection in a many developing nations. The World Health Organization estimates that there are around 21 million cases of typhoid fever per year and of these approximately 216,000 are fatal. Current typhoid vaccines are only moderately effective or unsafe for use by the very young or elderly. Research in our laboratory focuses on understanding the activation of innate and adaptive immune responses to Salmonella with a view to development of novel typhoid vaccines.

CD4 T cells and antibody are responsible for providing protective immunity to Salmonella infection and our laboratory is interested in understanding how these adaptive responses are initiated and develop in vivo. We have developed reagents to physically track Salmonella-specific T cells and are particularly interested in the activation of these cells in the intestine. Our recent studies have examined mucosal dendritic cell populations, defined by chemokine receptor expression, and the role that these cells play in mediating T cell activation to mucosal pathogens.

A number of years ago, we identified Salmonella flagellin as a target of the innate and adaptive immune system during Salmonella infection. Flagellin is an unusual antigen that can be recognized by Salmonella-specific CD4 T cells and is also recognized by the innate pattern recognition receptor TLR-5. Flagellin may therefore possess unique vaccine capabilities when used as a sub-unit vaccine or vaccine adjuvant. Our laboratory is actively exploring the use of flagellin as a vaccine adjuvant, and determining how flagellin activates innate immune responses in vivo.

Selected Recent Publications:

• Griffin, A. Baraho-Hussan, D., and S.J. McSorley. (2009) Successful treatment of bacterial infection hinders development of acquired immunity. J. Immunol. (In press)

• Srinivasan, A., Nanton, M., Griffin, A., and S.J. McSorley. (2009) In vivo culling of activated CD4 T cells driven by Salmonella virulence genes. J. Immunol. 182:7838.

• Salazar-Gonzalez, R.M., A. Srinivasan, A. Griffin, G. Muralimohan, J.M. Ertelt, R. Ravindran, A.T. Vella, and S.J. McSorley. (2007) Salmonella flagellin induces bystander activation of splenic dendritic cells and hinders bacterial replication in vivo. J. Immunol. 179:6169.

• Ravindran, R., L. Rusch, A. Itano, M.K. Jenkins, and S.J. McSorley. (2007) CCR6-dependent recruitment of blood phagocytes is necessary for rapid CD4 T cell responses to local bacterial infection. Proc. Natl. Acad. Sci. 104:12075.

• Srinivasan, A., R. Salzar-Gonzalez, M. Jarcho, M.M. Sandau, L. Lefrancois, and S.J. McSorley. (2007) Innate immune activation of CD4 T cells in Salmonella-infected mice is dependent on IL-18. J. Immunol. 178:6342.

• Srinivasan, A., and S.J. McSorley. (2007) Pivotal Advance: Suppression of CD4 T cell activation during murine typhoid following secondary exposure to LPS. J. Leuk. Biol. 81:403.

• Salazar-Gonzalez, R.M., J.H. Niess, D.J. Zammit, R. Ravindran, A. Srinivasan,J.R. Maxwell, T. Stoklasek, R. Yadav, I.R. Williams, X. Gu, B.A. McCormick,M.A. Pazos, A.T. Vella, L. Lefrancois, H-C. Reinecker, and S.J. McSorley. (2006) CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity 24:623-632.
  
  Last modified on: June 8, 2009