Activation of the alternative complement pathway by mannose-binding lectin via a C2-bypass pathway

Area of Science:

• Immunology
• Complement System Biology

Background:

• Mannose-binding lectin (MBL) is a key initiator of the lectin pathway in the complement system.
• MBL functions by binding to pathogen-associated molecular patterns and forming complexes with MBL-associated serine proteases (MASPs).

Purpose of the Study:

• To investigate the mechanisms by which MBL activates the alternative complement pathway.
• To determine if MBL-mediated complement activation is ligand-dependent and involves distinct pathways.

Main Methods:

• The study analyzed MBL's interaction with Salmonella serogroup C-specific oligosaccharide and mannan.
• Complement activation assays were performed to assess the involvement of MASP-2, C2, and C4 in MBL-mediated pathways.

Main Results:

• MBL binding to Salmonella serogroup C-specific oligosaccharide activated the alternative pathway via a C2-bypass mechanism, notably without MASP-2, C2, or C4.
• In contrast, mannan-bound MBL activated the alternative pathway through a C2-bypass pathway that necessitated MASP-2 and C4.

Conclusions:

• MBL can trigger complement activation through at least two distinct C2-bypass pathways.
• The specific ligand bound by MBL dictates the subsequent complement activation pathway, highlighting a versatile role for MBL in innate immunity.