The contribution of dendritic cells to infection and vaccine development for Streptococcus pyogenes

• Applicant: Dr. Lea Alessandra Tölken
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570286456

Streptococcus pyogenes is a human-specific bacterial pathogen responsible for a substantial burden of human disease with an estimated 18.1 million infections annually. This pathogen is primarily found as an asymptomatic commensal on human skin and the upper respiratory tract. S. pyogenes disease manifestations range from mild, superficial infections like pharyngitis (strep throat, approx. >600 million cases annually) to invasive, life-threatening infections like necrotizing skin and soft tissue infections. In addition, repeated S. pyogenes infections can lead to post-infection autoimmune sequelae, e.g. rheumatic heart disease, representing additional risks of otherwise uncomplicated infections. Overall, S. pyogenes infection is estimated to be responsible for >500,000 deaths per year, making this pathogen one of the top ten infectious disease pathogens for human mortality. Despite good susceptibility to common antibiotics and low occurrence of antibiotic resistance, S. pyogenes remains a significant healthcare burden, with no commercial vaccine available. In recent years, increased incidences of S. pyogenes infection and new, highly virulent sublineages have renewed interest in vaccine development. During colonization of the upper respiratory tract, S. pyogenes encounters a broad range of host cells. One major type of innate immune cells present in the upper respiratory tract are dendritic cells (DCs). These antigen-presenting cells have a central role in inducing a pathogen-specific immune response and are implicated in the development of long-lasting and effective vaccines. DCs process antigens and migrate to secondary lymphoid organs, where they present the antigens to T cells via MHC molecules to evoke an antigen-specific immune response. However, data on S. pyogenes-DC interaction is scarce, leaving many open questions in our understanding of the role of DCs in S. pyogenes infection. Understanding how DCs respond to S. pyogenes infection in the nasopharynx and how different virulence factors modulate this response is crucial for understanding how this pathogen adapts to its niche. In addition, this knowledge can contribute to developing an effective S. pyogenes vaccine. To address this, this proposal aims to conduct comprehensive phenotyping of DCs post nasopharyngeal S. pyogenes infection, using a humanized mouse model capable of replicating human upper respiratory tract infections. In addition, the contribution of key S. pyogenes virulence factors in the bacteria-DC interaction will be evaluated. The generated knowledge will then be used to help with vaccine development to prevent streptococcal experimental nasopharyngeal infection by using the DC cytokine response as endogenous adjuvants.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor John McCormick