Streptococcus agalactiaeInfection of a Reconstructed Human Respiratory Epithelium Revealed Infection and Host Response Characteristics by Different Serotypes

Background: Streptococcus agalactiae poses a significant threat to neonatal health, causing morbidity and mortality when transmitted from the maternal vagina to the newborn's respiratory tract. Among its various strains, serotype III is predominant in severe neonatal infections in Asia. However, the mechanisms of pathogenesis and host responses underlying serotype-specific disease outcomes remain poorly understood.

Methods: This study employed 2D airway epithelial organoids as a host model to investigate the progression of S. agalactiae respiratory tract infections across four serotypes. RNA and ATAC analyses were used to identify differentially expressed genes and related pathways.

Results: S. agalactiae infection triggered inflammatory responses in differentiated airway epithelia, particularly increasing the expression of genes linked to innate immunity. Serotype III elicited stronger immune responses compared to other serotypes. The SLC2A3 gene demonstrated upregulated expression and increased chromatin accessibility specific to serotype III infection.

Conclusions: Neonates predominantly clear S. agalactiae infections through immune detection and opsonophagocytosis. These findings highlight the importance of patient triage based on serotype variations. Developing therapeutic candidates targeting invasive serotypes to enhance OPK titers may be crucial. Furthermore, serotype III infection may induce apoptosis via Ferroptosis.