It has remained a longstanding mystery why some children are susceptible to recurrent tonsillitis. Tonsillectomies are the most common pediatric surgery in America, with recurrent tonsillitis associated with S. pyogenes (group A streptococcus, GAS) being a primary cause. We have preliminary data that there is an immunological basis for recurrent streptococcal tonsillitis. Antibody responses are a central part of the immune system. T follicular helper CD4 T cells (Tfh cells) are required for germinal centers, and thus the majority of high affinity antibody responses. Tfh cells have important roles in protection from infectious diseases. Much remains to be learned about Tfh cells. We have developed a novel method for quantifying pathogen-specific Tfh cells, the activation immune marker (AIM) assay. The goal of this proposal is to ascertain the immunologic mechanisms tied to recurrent strep throat, and the GAS virulence factors that cause recurrent tonsillitis disease. Completion of this study could help identify children who are likely to be susceptible to recurrent strep throat, and mechanistics studies propsed herein could allow for rational design of countermeasures to prevent the disease in the future.

Public Health Relevance

Tonsillectomies are the most common pediatric surgery in America, with recurrent tonsillitis associated with S. pyogenes (group A streptococcus, GAS) being a primary cause. It has remained a longstanding mystery why some children are susceptible to recurrent tonsillitis. We have preliminary data that there is an immunological basis for recurrent streptococcal tonsillitis, including antibody and T follicular helper (Tfh) CD4 T cell defects. Antibody responses are a central part of the immune system; T follicular helper CD4 T cells (Tfh cells) are required for germinal centers, and thus the majority of high affinity antibody responses. This proposal aims to understand the immunological and pathogen underpinnings of recurrent tonsillitis disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI135193-01A1
Application #
9596689
Study Section
Immunity and Host Defense (IHD)
Program Officer
Ferguson, Stacy E
Project Start
2018-06-14
Project End
2023-05-31
Budget Start
2018-06-14
Budget End
2019-05-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
La Jolla Institute
Department
Type
DUNS #
603880287
City
La Jolla
State
CA
Country
United States
Zip Code
92037