Interaction of lectin pathway of complement-activating pattern recognition molecules with mycobacteria

Area of Science:

• Immunology
• Microbiology
• Complement System

Background:

• Mannose-binding lectin (MBL) is a key initiator of the lectin pathway (LP) of complement.
• Mycobacteria, including Mycobacterium tuberculosis (MTB), are recognized by host immune factors.
• The role of MBL and other lectins in recognizing and interacting with mycobacteria requires further elucidation.

Purpose of the Study:

• To investigate the interaction between MBL, ficolins, and various mycobacterial species.
• To determine the role of these lectins in activating the complement lectin pathway and enhancing phagocytosis.
• To identify mycobacterial components involved in lectin-mediated recognition and complement activation.

Main Methods:

• Recognition assays using MBL and ficolins (ficolin-1, -2, -3) against slow-growing mycobacteria (MTB, M. bovis, M. kansasii, M. gordonae) and M. smegmatis.
• Assessment of complement lectin pathway activation and enhancement of phagocytosis.
• Western blot analysis to identify mycobacterial cell components involved in LP activation, focusing on mannosylated lipoarabinomannan (ManLAM).

Main Results:

• MBL recognized pathogenic and non-pathogenic mycobacteria, activating the LP and enhancing M. tuberculosis phagocytosis.
• Ficolin-3 interacted with M. tuberculosis, M. bovis, and M. kansasii; ficolin-1 interacted with M. tuberculosis and M. bovis.
• Binding of MBL and ficolin-3 promoted bacterial agglutination and phagocytosis, with mannosylated lipoarabinomannan (ManLAM) identified as a key LP-activating component.

Conclusions:

• MBL and ficolins, particularly ficolin-3, play significant roles in the host's interaction with mycobacteria via the complement lectin pathway.
• These lectin-mycobacteria interactions lead to enhanced bacterial clearance mechanisms like phagocytosis.
• Ficolins may act as disease modifiers in mycobacterial infections, highlighting their clinical significance.