Group A Streptococcus (GAS) represents a major global health threat. Beyond acute infections, GAS can lead to severe complications, such as rheumatic fever and rheumatic heart disease, emphasizing the need to understand immune responses at the primary site of infection: tonsillar tissue. Despite decades of vaccine development, progress has been limited by the absence of reliable human models that capture the complexities of immune responses. To address these gaps, we have taken a multifaceted approach to investigate the immunological landscape in both patient biopsies and using novel in vitro models.
We performed high-dimensional spatial immune phenotyping on tissue sections using the MACSima platform. Tonsillar biopsies were obtained from nine patients with sleep apnea, chronic tonsillitis, and recurrent tonsillitis. Targeting 13 immune markers, we identified distinct stromal compartment, germinal centers and distribution of specific immune cells in the tissue. Comparative analysis showed no significant differences in immune cell frequencies between groups, prompting ongoing investigations into micro-niches such as the germinal centers and epithelium.
To complement the biopsy analysis, we are developing advanced in vitro models, including ex vivo tonsillar models and organotypic 3D systems incorporating immune cells. These models will enable precise simulations of GAS infection and antigen stimulation, overcoming current preclinical limitations and providing a controlled environment to study host-pathogen interactions.
Our study provides insights into the tonsillar immune landscape and by integrating high-resolution spatial profiling with innovative in vitro models, we establish a powerful framework for accelerating vaccine development and advancing our understanding of immune susceptibility.