What is an opsonin?

What is an Opsonin?

An opsonin is a protein that binds to the surface of pathogens or other particles, enhancing their recognition and phagocytosis by immune cells through specific receptors on phagocytes. 1

Definition and Function

• Opsonins are soluble, extracellular proteins that coat foreign particles (like bacteria) or apoptotic cells, marking them for recognition and clearance by phagocytic cells 2
• They act as molecular bridges between the target cell/particle and the phagocyte, facilitating efficient phagocytosis 3
• Opsonization is a key process in innate immunity that allows for rapid clearance of pathogens before adaptive immunity develops 1

Types of Opsonins

There are several classes of opsonins:

1. Classical opsonins:

   • Antibodies (immunoglobulins) - particularly IgG, which binds to Fc receptors on phagocytes 3
   • Complement proteins - especially C3b and C4b, which bind to complement receptors 1
   • Pattern recognition receptors - secreted proteins that recognize pathogen-associated molecular patterns 2

2. Recently identified opsonins:

   • Calreticulin - a lectin that can bind lipopolysaccharide (LPS) on bacterial surfaces 2
   • Galectin-3 - another lectin that binds LPS and enhances bacterial phagocytosis 2
   • Ficolin-A (rodent ortholog of human L-ficolin) - can bind and opsonize fungal pathogens like Aspergillus fumigatus 4
   • Beta-2-glycoprotein I (β2GPI) - recognizes phosphatidylserine on apoptotic cells 1
   • C-reactive protein (CRP) - binds to phosphocholine on microbial surfaces 1
   • Thrombospondin I - facilitates clearance of apoptotic cells 1

Mechanism of Action

• Opsonins recognize and bind to specific structures on target surfaces:

  • Antibodies bind to specific antigens 3
  • Complement proteins bind to microbial surfaces or antibody-antigen complexes 1
  • Lectins like calreticulin and galectin-3 bind to carbohydrate structures like LPS 2

• Once bound to the target, opsonins present recognition sites for receptors on phagocytes:

  • Fc portions of antibodies are recognized by Fc receptors 3
  • Complement fragments are recognized by complement receptors 1
  • Other opsonins may be recognized by specific receptors like LRP1 (for calreticulin) or MerTK (for galectin-3) 2

Biological Significance

• Opsonization significantly enhances phagocytosis efficiency:

  • Artificial opsonins have been shown to increase neutrophil phagocytosis of Staphylococcus epidermidis by approximately 2-fold 5
  • Opsonization can increase oxidative burst in neutrophils, enhancing bacterial killing 5

• In the brain, where traditional opsonins have limited access, microglia release alternative opsonins like calreticulin and galectin-3 when activated by bacterial components 2

• Defects in opsonization can lead to immune dysfunction:

  • C1q deficiency (a complement component that acts as an opsonin) is associated with development of autoimmunity in mice 1
  • Patients with congenital nephrotic syndrome are prone to infections by encapsulated bacteria due to urinary losses of IgG and complement opsonins 6

• Many tumors are rich in tumor-associated macrophages, and protein coronas around nanoparticles can act as opsonins, triggering phagocytosis through binding to receptors on these macrophages 6

Clinical Applications

• Understanding opsonization has led to therapeutic strategies:

  • Artificial opsonins are being developed as potential immunostimulatory therapeutics to control infections caused by Gram-positive bacteria, especially those that are immune evasive or antibiotic-resistant 5
  • In nanomedicine, PEGylation of nanoparticles creates a hydrophilic layer that provides a steric barrier to opsonin adsorption, reducing clearance by the reticuloendothelial system and increasing circulation time 6

• Opsonization is particularly important in certain clinical contexts:

  • In congenital nephrotic syndrome, loss of opsonins increases susceptibility to infections by encapsulated bacteria 6
  • In tumor microenvironments, opsonization affects nanoparticle-based drug delivery systems 6

Opsonins in Disease

• Abnormal opsonization of apoptotic cells can contribute to autoimmune diseases:

  • Apoptotic cells opsonized by autoantibodies can trigger pro-inflammatory responses in macrophages 1
  • Surface changes on apoptotic cells, such as exposure of phosphatidylserine, can activate opsonins like complement and β2GPI 1

• Opsonins can modulate inflammatory responses:

  • Ficolin-A opsonization of Aspergillus fumigatus can decrease production of pro-inflammatory cytokines (IL-8, IL-1β, IL-6, IL-10, TNF-α) from monocyte-derived macrophages 4