Five million people are annually diagnosed with streptococcal pharyngitis, and 1200-1500 die annually from complications of group A streptococcal (GAS) infections in the United States alone. The over all goal of this projection is to understand the cellular and immunological reason that up to a third of children vigorously treated for pharyngitis continue to shed streptococci and why even more fail to develop a measurable immune response. Our in investigation will make use of a well-developed intranasal infection murine model to mimic infection of human tonsils. Preliminary results show that GAS have an efficient tropism for lymphoid tissue (NALT) beneath nasal passages of BalBc. Adoptive transfer of transgenic, naive ovalbumin specific CD4 T cells will be used to study the T cell based immune response in vivo following intranasal infection of mice with wild type and mutant strains of GAS that expresses the Ova antigen on their surface. Experiments will determine impact of infection on the antigen specific T cell response in NALT and other lymphoid organs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI059533-04
Application #
7323232
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Rubin, Fran A
Project Start
2004-12-15
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2009-11-30
Support Year
4
Fiscal Year
2008
Total Cost
$273,089
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Dileepan, Thamotharampillai; Linehan, Jonathan L; Moon, James J et al. (2011) Robust antigen specific th17 T cell response to group A Streptococcus is dependent on IL-6 and intranasal route of infection. PLoS Pathog 7:e1002252
Wang, Beinan; Dileepan, Thamotharampillai; Briscoe, Sarah et al. (2010) Induction of TGF-beta1 and TGF-beta1-dependent predominant Th17 differentiation by group A streptococcal infection. Proc Natl Acad Sci U S A 107:5937-42
Hyland, Kendra A; Brennan, Robert; Olmsted, Stephen B et al. (2009) The early interferon response of nasal-associated lymphoid tissue to Streptococcus pyogenes infection. FEMS Immunol Med Microbiol 55:422-31
Hyland, Kendra A; Wang, Beinan; Cleary, P Patrick (2007) Protein F1 and Streptococcus pyogenes resistance to phagocytosis. Infect Immun 75:3188-91