The adaptive immune response to mucosal pathogens is still poorly understood, limiting the development of new vaccines for important human pathogens such as the category B bioterrorism agent Salmonella. I propose to use newly developed reagents to examine the Salmonella-specific CD4 T cells activation and memory in the intestinal mucosa and systemic tissues.
The specific aims of this proposal are:
Aim 1. Determine whether differential expression of Salmonella proteins in different locations allows priming of site-specific CD4 T cells.
Aim 2. Examine whether Salmonella-specific memory CD4 T cell development is impaired after rapid clearance of virulent bacteria. My preliminary data demonstrate that I can develop novel MHC class-II tetramer reagents to track the mucosal and systemic Salmonella-specific T cell response in vivo. My two specific aims will use cutting-edge technology, to examine the priming, and memory development of endogenous Salmonella-specific T cells for the first time.
Typhoid is a potentially fatal disease caused by oral Salmonella infection and recognized as a potential bioterrorist threat in the US. This proposal will examine the protective CD4 T cell response to this organism using a mouse model of Salmonella infection and newly developed immunological tools to detect mucosal and systemic responses. This proposal will therefore increase our understanding of how these protective CD4 T cells are activated and function in the face of mucosal bacterial infection.
|Nanton, Minelva R; Lee, Seung-Joo; Atif, Shaikh M et al. (2015) Direct visualization of endogenous Salmonella-specific B cells reveals a marked delay in clonal expansion and germinal center development. Eur J Immunol 45:428-41|
|Nanton, Minelva R; Way, Sing Sing; Shlomchik, Mark J et al. (2012) Cutting edge: B cells are essential for protective immunity against Salmonella independent of antibody secretion. J Immunol 189:5503-7|
|Lee, Seung-Joo; Liang, Li; Juarez, Silvia et al. (2012) Identification of a common immune signature in murine and human systemic Salmonellosis. Proc Natl Acad Sci U S A 109:4998-5003|
|Ertelt, James M; Johanns, Tanner M; Mysz, Margaret A et al. (2011) Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection. Immunology 134:487-97|