Pneumococcal transmission is driven by TNFR2+ regulatory T-cells

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Pneumococcal serotype 1 (sequence type 217) causes severe invasive disease outbreaks in Sub-Saharan Africa.
• Understanding ST217 transmission is crucial for developing effective vaccines and therapies.

Purpose of the Study:

• To investigate the transmission dynamics of the hypervirulent pneumococcal strain ST217.
• To identify host immune factors influencing ST217 transmission.

Main Methods:

• Utilized an adolescent mouse model to study pneumococcal transmission dynamics.
• Analyzed the role of regulatory T-cells (Tregs) and their interaction with immune cells during colonization.

Main Results:

• TNF receptor-2 (TNFR2)-positive Tregs were found to promote ST217 transmission by suppressing IL-17A-producing γδT and Th17 cells, impairing neutrophil-mediated clearance.
• This Treg-mediated immunosuppression increases pneumococcal carriage density and nasal shedding.
• The strain-specific effect is driven by pneumolysin, with low-activity pneumolysin in serotype 23F leading to impaired Treg responses and enhanced clearance.

Conclusions:

• TNFR2-positive Tregs play a critical, unexpected role in the transmission of hypervirulent pneumococci.
• Targeting TNFR2+ Treg-mediated suppression presents a potential strategy for controlling pneumococcal outbreaks.