Researchers have identified immunologic factors that predispose certain children to recurrent tonsil infections caused by group A streptococci bacteria. While nearly everyone is exposed to strep bacteria during childhood, only some children develop recurrent tonsillitis. New findings from an NIAID-supported study published today in Science Translational Medicine uncover immune responses linked to recurrent tonsillitis and suggest a potential strategy for development of a vaccine to prevent strep infections.
Recurrent tonsil infections can be painful and challenging to live with. While antibiotics help clear the infections, doctors may recommend that children with recurrent tonsillitis have their tonsils removed. To address the question of why some children are susceptible to recurrent infections, researchers from the La Jolla Institute for Immunology examined immunological characteristics of the tonsils of children aged 5 to 18 years living in the San Diego area. Over the course of the study, they compared tonsil samples from 66 children who had their tonsils removed for recurrent strep infections with those from 80 children who had tonsillectomies for other reasons, such as to relieve sleep apnea.
The researchers found that the tonsils of children with recurrent tonsillitis harbored higher frequencies of a novel population of T follicular helper cells, or Tfh cells. Tfh cells typically play a critical role in protective immunity by helping B cells mature to produce antibodies that recognize specific pathogen components, or antigens. But instead of assisting B-cell maturation, this newly identified population of Tfh cells in the tonsils of children with recurrent infections is capable of killing B cells, limiting their ability to generate protective antibodies against strep bacteria. The scientists discovered that a strep antigen called SpeA activates these unusual Tfh cells, causing them to secrete B-cell-destroying proteins.
The researchers moreover found lower levels of antibodies against SpeA in blood samples from children with recurrent tonsillitis. Levels of antibodies against a different strep antigen, however, were similar among kids with and without recurrent tonsil infections. This suggests that although all the children had been exposed to strep bacteria, only those susceptible to recurrent tonsillitis had aberrant immune responses to SpeA. Previous studies have indicated that anti-SpeA antibodies are protective against strep infections, suggesting that lower levels of these antibodies may increase susceptibility to repeated infections.
Understanding the factors that influence susceptibility to recurrent tonsillitis will help guide development of prevention strategies. Specifically, the researchers suggest that a vaccine based on an inactivated version of SpeA potentially could protect against strep throat and recurrent tonsillitis. Such a vaccine would need to elicit production of antibodies against SpeA and avoid triggering the B-cell-killing function of Tfh cells. Development of a safe and effective vaccine against group A streptococci could reduce the number of antibiotic treatments and surgeries needed to address recurrent tonsil infections, as well as alleviate the general burden of childhood strep throat disease.
To learn more about NIAID-supported vaccine development efforts, see Group A Streptococcus Vaccine Research. For information about diagnosis and treatment of strep throat, see CDC’s Strep Throat: All You Need to Know.
JM Dan et al. Recurrent Group A streptococcus tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells. Science Translational Medicine DOI: 10.1126/scitranslmed.aau3776 (2019).