Abstract

Staphylococcus aureus and Group A Streptococcus (GAS) are common occupants of the tonsils and many strains produce potent exotoxins (mitogens) that directly target T cells, which could be a driver for tonsillar hyperplasia. Tonsil tissues from 41 patients were tested for these bacteria in conjunction with profiling of B and T cells by flow cytometry. S. aureus and GAS were detected in tonsil tissue from 44% and 7%, respectively, of patients by bacteriological culture; immuno-histology showed bacteria in close proximity to both B and T lymphocytes. The presence of tonsillar S. aureus did not alter B or T cell populations, whereas peripheral blood mucosal-associated invariant T (MAIT) cells were significantly increased in S. aureus culture positive individuals (p < 0.006). Alterations of tonsil CD4+ TCR Vβ family members relative to peripheral blood were evident in 29 patients. Three patients had strong TCR Vβ skewing indicative of recent exposure to superantigens, their tonsils contained mitogenic bacteria, and supernatants from these bacteria were used to partially recapitulate the skewing profile in vitro, supporting the notion that superantigens can target tonsillar T cells in situ. Tonsils are a reservoir for superantigen-producing bacteria with the capacity to alter the composition and function of key immune cells.

Highlights

  • A diverse range of microbes encompassing both commensal and pathogenic organisms have been isolated from human tonsils

  • This study extends these observations in a new cohort of patients, using additional techniques to confirm the location of S. aureus or Group A Streptococcus (GAS) within tonsil tissues and a comparison of matched tonsil and peripheral blood TCR Vβ profiles to verify local skewing of T cells

  • This study builds on an earlier finding that skewing of TCR Vβ subsets is relatively common in tonsillar tissue [24], demonstrating that selective expansion of TCR Vβ populations is localized to the tonsillar tissue [24], demonstrating that selective expansion of TCR Vβ populations is localized to the tonsils and that it is possible to partially reproduce patient TCR Vβ profiles in vitro using supernatants tonsils and that it is possible to partially reproduce patient TCR Vβ profiles in vitro using from their own mitogenic S. aureus or GAS strains

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Summary

Introduction

A diverse range of microbes encompassing both commensal and pathogenic organisms have been isolated from human tonsils. There is ongoing interest in the flora associated with these tissues because enlargement of the tonsils (tonsillar hyperplasia) is a common indication for surgery. The requirement for surgery can arise either due to tonsillar hyperplasia causing conditions such as obstructive sleep apnea (OSA) or from recurrent tonsillitis (RT), which is caused by repeated infections. A tonsillectomy is one of the most frequent surgical procedures performed on children, with a growing proportion performed to treat sleep apnea disorders such as OSA [1]. There are significant direct medical costs as well as an indirect economic burden associated with tonsillar hyperplasia [2,3]. Of particular concern is the high usage of antibiotics to treat these conditions

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