Superantigen Interactions in Streptococcal Tonsillitis
Author(s)
Davies, Frances Joan
Type
Thesis
Abstract
Streptococcus pyogenes is the commonest cause of bacterial throat infections, and asymptomatic throat carriage acts as an important reservoir for invasive soft tissue infections. Despite the high rates of infection little is known about the immunology of streptococcal throat infections. Superantigens have been identified as one of the bacterial virulence factors associated with the establishment of streptococcal throat infections. This PhD investigates superantigen expression both in vitro and in clinical disease, and the immune effects of superantigens in human tonsils.
Results:
The production of superantigens was assessed using quantitative RT-PCR and biological assays both directly from patient samples and from the corresponding strain in vitro. The presence of superantigens was demonstrated in tissues which cultured live bacteria. In vitro production of the superantigen SMEZ from throat strains was higher than from invasive strains.
Human tonsils were cultured as cell suspensions or solid block histocultures and stimulated with recombinant superantigens. There was a marked clonal T cell expansion and pro-inflammatory cytokine release in the presence of superantigens. There was apoptosis of tonsil B cells during co-culture with superantigens, with inhibition of IgG, IgA and IgM production. This corresponded with an alteration of the tonsil T cell phenotype from CXCR5 expressing T follicular helper cells to proliferating cells expressing high levels of the TNF receptor superfamily members OX40 and ICOS and the immune synapse signalling molecule SLAM.
Conclusions:
Superantigens are actively produced during clinical infection with S. pyogenes. They profoundly alter the functions of tonsil B and T cells in vitro, resulting in impaired immunoglobulin production.
Results:
The production of superantigens was assessed using quantitative RT-PCR and biological assays both directly from patient samples and from the corresponding strain in vitro. The presence of superantigens was demonstrated in tissues which cultured live bacteria. In vitro production of the superantigen SMEZ from throat strains was higher than from invasive strains.
Human tonsils were cultured as cell suspensions or solid block histocultures and stimulated with recombinant superantigens. There was a marked clonal T cell expansion and pro-inflammatory cytokine release in the presence of superantigens. There was apoptosis of tonsil B cells during co-culture with superantigens, with inhibition of IgG, IgA and IgM production. This corresponded with an alteration of the tonsil T cell phenotype from CXCR5 expressing T follicular helper cells to proliferating cells expressing high levels of the TNF receptor superfamily members OX40 and ICOS and the immune synapse signalling molecule SLAM.
Conclusions:
Superantigens are actively produced during clinical infection with S. pyogenes. They profoundly alter the functions of tonsil B and T cells in vitro, resulting in impaired immunoglobulin production.
Date Issued
2012
Date Awarded
2012-05
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Sriskandan, Shiranee
Publisher Department
Medicine: Department of Infectious Diseases and Immunity
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)