Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

The dynamic human systemic transcriptomic signature of Streptococcus pyogenes pharyngitis (119137)

Hannah R Frost 1 2 , Mei Du 1 , Natalie Caltabiano 1 , Michael See 1 , Yara Abo 1 3 , Mirana Ramialison 1 , Danika L Hill 4 , Fernando Rossello 1 , Andrew C Steer 1 2 3 , Joshua Osowicki 1 2 3
  1. Murdoch Children's Research Institute, Melbourne, VIC, Australia
  2. Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
  3. Infectious Diseases Unit, Department of General Medicine, Royal Children's Hospital, Melbourne, VIC, Australia
  4. Precision Vaccinology, Monash University, Melbourne, VIC, Australia

Background:

The advent of a Streptococcus pyogenes pharyngitis human challenge model has enabled unprecedented insight into pathways of pathogenesis and protection. Here, we explored the host systemic transcriptomic response to experimental infectious challenge, aiming to expand our understanding of critical early innate and adaptive immunity.

 

Methods:

Bulk RNA sequencing was performed on 128 whole blood samples collected from 25 healthy adults in the CHIVAS-M75 study, 19 of whom developed pharyngitis 48-96 hours after pharyngeal challenge with S. pyogenes. Differentially expressed genes (DEGs) from baseline were tracked daily, comparing participants with and without pharyngitis. We also compared these data to cross-sectional paediatric data. Outputs of gene set enrichment with blood transcriptional modules (BTMs) were compared to flow cytometry phenotypic changes.

 

Results:

A systemic transcriptomic signature was observed in CHIVAS-M75 participants with pharyngitis, with 9 DEGs 8-12 hours after challenge, 4,520 after 24 hours, and 12,441 after 48 hours. The DEGs matched findings in children, with 85.6% (n=458) of previously defined paediatric S. pyogenes pharyngitis-specific DEGs also differentially expressed at the 48-hour timepoint. BTM analysis highlighted signals of neutrophil activation, early downregulation of T and B cell genes, and upregulation in innate immune cells and antigen presentation, consistent with previous immunophenotyping results.

 

Conclusion:

Experimental human pharyngitis in healthy adults is associated with a systemic transcriptomic signature similar to natural infection in children. Marked changes in gene expression occur from 48 hours after infectious challenge, highlighting the capacity of the human model to investigate the critical early stages of streptococcal infection and immunity.