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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI091298-03
Application #
8287643
Study Section
Special Emphasis Panel (ZRG1-DKUS-D (29))
Program Officer
Adger-Johnson, Diane S
Project Start
2010-07-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$34,883
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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
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