Impaired upper respiratory tract barrier function during postnatal development predisposes to invasive pneumococcal...

Area of Science:

• Immunology
• Microbiology
• Developmental Biology

Background:

• Infants are vulnerable to invasive respiratory and gastrointestinal infections.
• Understanding age-dependent mechanisms of bacterial spread is crucial for pediatric health.

Purpose of the Study:

• To investigate the mechanisms underlying increased susceptibility to Streptococcus pneumoniae (Spn) in infant mice.
• To elucidate age-dependent bacterial dissemination from the upper respiratory tract (URT) mucosa.

Main Methods:

• Developed an infant mouse model for Spn infection.
• Utilized molecular barcoding to track bacterial dissemination.
• Performed transcriptional profiling of the URT epithelium.
• Assessed URT barrier permeability and mucociliary clearance.

Main Results:

• Infant mice exhibited decreased survival and increased Spn bacteremia compared to adults.
• Bacterial dissemination was not linked to immune cell infiltration or specific inflammatory pathways.
• Infant URT epithelium failed to upregulate tight junction genes, indicating impaired barrier function.
• Increased URT permeability and delayed mucociliary clearance were observed in infant mice.

Conclusions:

• A critical window of vulnerability exists during early postnatal development.
• Altered mucosal barrier function, specifically impaired tight junctions and delayed clearance, facilitates bacterial dissemination in infants.
• Findings highlight the importance of mucosal barrier maturation in preventing invasive infections.