Ficolin-2 Lectin Complement Pathway Mediates Capsule-Specific Innate Immunity Against Invasive Pneumococcal Disease

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• The lectin pathway (LP) of complement's role in protective immunity is debated.
• Specific microbial ligand interactions triggering LP responses require clarification.

Purpose of the Study:

• To investigate the interaction between ficolin-2 and Streptococcus pneumoniae.
• To determine if this interaction elicits a protective complement response.

Main Methods:

• Fluorescent microscopy was used to visualize ficolin-2 binding to S. pneumoniae serotype 11A.
• The role of the wcjE gene in ficolin-2 ligand expression was assessed through mutagenesis.
• Bacterial killing assays and complement deposition studies were performed.

Main Results:

• Ficolin-2 specifically binds to S. pneumoniae serotype 11A capsule polysaccharide, dependent on the wcjE gene.
• This binding triggers complement deposition and opsonophagocytosis, leading to bacterial killing.
• Mutations in wcjE abrogated ficolin-2 binding and bacterial killing, with evidence of microevolution towards deficient strains during invasive pneumococcal disease.
• Ficolin-2 did not bind to pneumococcal teichoic acid or other non-capsule structures.

Conclusions:

• The ficolin-2/LP axis provides innate, serotype-specific protection against invasive pneumococcal disease.
• The wcjE gene and its dependent epitopes are crucial for ficolin-2 recognition and antibacterial activity.
• Reevaluation of the LP's impact requires a glycopolymer-specific approach due to limited carbohydrate ligands.