Inhibition of the Classical Pathway of Complement Activation Impairs Bacterial Clearance during Enterococcus faecalis...

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Enterococcus faecalis infections pose a global health threat.
• The complement system, with its classical, lectin, and alternative pathways, is crucial for pathogen defense.
• The role of the classical pathway (CP) in Enterococcus faecalis infection immunity is not well understood.

Purpose of the Study:

• To investigate the role of the classical pathway (CP) in host defense against Enterococcus faecalis.
• To evaluate the efficacy of blocking the CP using anti-C1s-A Fab fragments in a mouse model.

Main Methods:

• Generation of Fab fragments targeting the C1s-A enzyme, a key component of the CP.
• In vitro assessment of Fab fragment ability to inhibit CP-mediated C3b and C4b deposition.
• In vivo evaluation of CP functional activity and Enterococcus faecalis bacterial clearance in treated mice.

Main Results:

• Anti-C1s-A Fab fragments effectively blocked CP-mediated C3b and C4b deposition in vitro.
• Administration of anti-C1s-A Fab fragments significantly inhibited CP activity in vivo.
• Treatment with anti-C1s-A Fab fragments markedly impaired bacterial clearance in mice infected with Enterococcus faecalis.

Conclusions:

• The classical pathway (CP) plays an essential role in host defense against Enterococcus faecalis infections.
• Inhibition of the CP via C1s-A blockade compromises the ability to clear Enterococcus faecalis.
• Targeting the CP represents a potential therapeutic strategy against Enterococcus faecalis infections.