Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis
Maren Seitz1, Andreas Beineke, Alena Singpiel
1Institute for Microbiology, University of Veterinary Medicine Hanover, Hanover, Germany.
Abstract:
Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-) mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3(-/-) mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3(-/-) mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3(-/-) blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR(-/-) mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity.
Insights
The complement system protects against invasive Streptococcus suis infections. This study shows the bacterial capsule is key for colonization and evading immune responses.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Streptococcus suis serotype 2 (S. suis) causes severe infections like septicemia and meningitis in piglets and humans.
- The role of the complement system in innate immunity against S. suis remains incompletely understood.
Purpose of the Study:
- To investigate the function of the complement system in innate immune defense against S. suis.
- To determine the contribution of S. suis capsule and suilysin to virulence and immune evasion.
Main Methods:
- Experimental infection of wild-type (WT), C3(-/-), and C5aR(-/-) mice with S. suis.
- Analysis of bacterial colonization, mortality, and pathogenesis.
- Flow cytometry for complement C3 deposition on bacteria.
- Ex vivo bacterial multiplication in murine blood.
Main Results:
- The complement system is crucial for protecting naive mice against invasive S. suis infection.
- S. suis mortality and meningitis in C3(-/-) mice were associated with WT but not unencapsulated strains.
- The bacterial capsule significantly contributes to upper respiratory tract colonization and evasion of complement-dependent immunity.
- Suilysin expression facilitates early disease onset and meningitis pathogenesis.
- Complement component C3 deposition was observed on S. suis WT bacteria, but less intensely than on unencapsulated mutants.
- Bacterial multiplication in blood depended on the capsule, not suilysin.
- Immune cell activation via C5aR is important for defense against S. suis.
Conclusions:
- The complement system plays a vital role in defense against mucosal S. suis serotype 2 infections.
- The S. suis capsule is essential for colonization and contributes to immune evasion.
- Complement-mediated opsonization and C5aR-dependent immune cell activation are critical defense mechanisms.
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