Streptococcal protein H forms soluble complement-activating complexes with IgG, but inhibits complement activation by...

Area of Science:

• Immunology
• Microbiology
• Complement System

Background:

• Streptococcus pyogenes protein H binds IgG's Fc region and can be released from bacteria.
• Post-streptococcal diseases like glomerulonephritis and rheumatic fever involve immune complexes and autoimmunity.
• The role of released protein H in complement activation and host-parasite interactions is unclear.

Purpose of the Study:

• To investigate the effect of protein H on complement activation.
• To determine the mechanism of complement activation by protein H-IgG complexes.
• To assess the role of protein H in complement regulation on bacterial surfaces and in soluble complexes.

Main Methods:

• Protein H was added to human serum, and complement activation was measured by C3 cleavage.
• Complement-depleted serum reconstituted with specific complement proteins was used to identify activation pathways.
• Binding assays investigated protein H's effect on C1q-IgG interaction and C3 deposition on immobilized IgG and bacterial surfaces.

Main Results:

• Protein H induced dose-dependent C3 cleavage in human serum, dependent on IgG and the classical complement pathway.
• Soluble protein H-IgG complexes activated complement, but protein H inhibited activation on immobilized IgG by blocking C1q binding.
• Protein H reduced C3 deposition on bacterial surfaces, suggesting a role in immune evasion.

Conclusions:

• Released protein H-IgG complexes can activate complement, potentially contributing to immunological complications of streptococcal infections.
• Protein H inhibits complement activation on the bacterial surface, a mechanism important for host-parasite relationships.
• The dual role of protein H in complement activation (soluble complexes) and inhibition (bacterial surface) warrants further investigation.