What pathogens activate the lectin pathway?

Pathogens That Activate the Lectin Pathway of Complement

The lectin pathway of complement is primarily activated by mannose-binding lectin (MBL), ficolins, and collectins recognizing carbohydrate patterns on microbial surfaces including bacteria, viruses, fungi, and parasites. 1, 2

Key Activating Pathogens

Bacterial Pathogens

• Staphylococcus aureus - Recognized through cell wall components 3
• Staphylococcus epidermidis - Activates via glycerol teichoic acid and polysaccharide intercellular adhesion 3
• Streptococcus species - Including S. equinus and S. viridans via glycosyl transferases 3
• Enterococcus faecalis - Through aggregation substance (Agg) and endocarditis-associated antigen A 3
• Listeria monocytogenes - Via alginate structures 3
• Pseudomonas aeruginosa - Through hyphal wall proteins 3
• Coxiella burnetii - Activates the lectin pathway during Q fever infection 3
• Yersinia pestis - Plague-causing bacterium recognized by MBL 3

Viral Pathogens

• Coronavirus - Including SARS-CoV, which binds to L-SIGN receptors and activates the lectin pathway 3
• Encephalitis viruses - Including alphaviruses from the Togaviridae family 3

Fungal Pathogens

• Candida albicans - Via mannose-containing structures on cell walls 3
• Candida parapsilosis - Recognized through cell surface carbohydrates 3

Mechanism of Lectin Pathway Activation

1. Recognition Phase:

   • Pattern recognition molecules (MBL, ficolins, collectin-11) bind to carbohydrate patterns on pathogen surfaces 2
   • Common targets include mannose, N-acetylglucosamine, and other sugar moieties 1

2. Activation Phase:

   • Upon binding, MBL-associated serine proteases (MASPs) undergo conformational changes
   • MASP-1 activates MASP-2
   • MASP-2 cleaves complement components C4 and C2 2
   • Formation of C3 convertase (C4b2a) occurs

3. Amplification and Effector Phase:

   • C3 convertase cleaves C3 into C3a and C3b
   • C3b opsonizes pathogens for phagocytosis
   • Formation of membrane attack complex leads to pathogen lysis 4

Clinical Significance

• Sepsis and Septic Shock: Lectin pathway activation contributes to inflammatory response during sepsis 5
• Recurrent Infections: Deficiencies in lectin pathway components increase susceptibility to infections 3
• Rheumatic Heart Disease: Lectin pathway activation may contribute to pathogenesis following streptococcal infections 4
• COVID-19: Lectin pathway may be involved in the inflammatory response to SARS-CoV-2 3

Pathogen Evasion Strategies

Many pathogens have evolved mechanisms to evade the lectin pathway:

• Molecular Mimicry: Pathogens disguise their surface structures to avoid recognition
• Proteolytic Degradation: Some pathogens produce proteases that degrade MBL and ficolins
• Recruitment of Host Regulators: Pathogens may bind host complement regulatory proteins 6

Clinical Applications

• Diagnostic Potential: Measuring lectin pathway components may help identify immunodeficiencies
• Therapeutic Targets: Modulation of the lectin pathway could be beneficial in infections where complement overactivation contributes to pathology
• Prophylaxis: In patients with complement deficiencies, antimicrobial prophylaxis may be indicated 3

Understanding which pathogens activate the lectin pathway has important implications for diagnosing immunodeficiencies and developing targeted therapies for infectious diseases.