The mucosal immune system is constantly exposed to a wide range of commensal and potentially pathogenic microbial species. This chronic exposure to inflammatory mediators and nonpathogenic organisms makes generation of an appropriate immune response critical in maintaining a balance between elimination of harmful pathogens and regulating responses to nonpathogenic organisms. While Listeria monocytogenes (LM) (a category B Biodefense priority pathogen) is one of the most widely utilized pathogens for examining T cell immune responses, little is known about induction of the mucosal CDS T cell response after oral infection. The overall hypothesis to be tested is that effector CDS T cell subsets are differentially regulated by mucosal environmental cues to promote rapid local protection. We will address this hypothesis using a new oral infection model that more closely mimics the human infection.
The specific aims of the project are:
Aim 1 : To define the anatomical events leading to generation of protective mucosal CDS T cell memory.
Aim 2 : To understand the dynamics of CDS T cell priming in response to oral bacterial infection.
Aim 3 : To define the mechanisms regulating development of protective mucosal CDS memory T cells. The studies proposed will examine the eariiest events of CDS T cell differentiation through memory T cell homeostasis and recall to secondary challenge. Examining the induction of effector T cells and the maintenance and recall of memory T cells to a bona fide gut pathogen that closely mimics human infection is critical for a better understanding of CDS T cell immunity in the intestinal mucosa. The knowledge gained from this proposal has broad application potential ranging from understanding the immune response to intestinal pathogens to mucosal vaccine designs.

Public Health Relevance

This project will define the parameters controlling the immune response to an intestinal bacterial infection transmitted through ingestion of the pathogen. The mouse model used recapitulates the human infection and therefore has direct relevance to understanding mucosal immunity and vaccination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI056172-08A1
Application #
8424000
Study Section
Special Emphasis Panel (ZAI1-PA-I (S1))
Project Start
2003-09-01
Project End
2018-04-30
Budget Start
2013-05-15
Budget End
2014-04-30
Support Year
8
Fiscal Year
2013
Total Cost
$440,235
Indirect Cost
$129,763
Name
University of Connecticut
Department
Type
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
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Pham, Oanh H; McSorley, Stephen J (2015) Protective host immune responses to Salmonella infection. Future Microbiol 10:101-10

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