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Granulocyte phagocytosis of Streptococcus pneumoniae in properdin-deficient serum
Abstract:
Properdin (P)-deficient human serum containing type-specific anticapsular antibodies and having an intact classical pathway of complement did not support efficient granulocyte phagocytosis of Streptococcus pneumoniae serotypes 6A, 14, 19F, 23F, or 35 in an opsonophagocytic assay. Compared with pooled control serum, the difference was most pronounced for serotypes 14 and 23F and at a final serum concentration of 16%. The reduced phagocytic killing of S. pneumoniae serotype 23F in P-deficient serum was due rather to defective opsonization than to impaired intracellular killing. The uptake of C3 by the serotype 23F strain was found to be low in P-deficient serum. The addition of native P promoted C3 fixation as well as opsonization. The activity of P was abolished by heat treatment (56 degrees C, 30 min). Experiments with Mg EGTA to block C1 activation suggested that serotype 23F pneumococci were more dependent on the classical pathway for opsonization than were serotype 35 pneumococci, which appear to be partly opsonized through the alternative pathway alone.
Insights
Properdin deficiency impairs granulocyte phagocytosis of Streptococcus pneumoniae by hindering complement component 3 (C3) opsonization, particularly for specific serotypes. Adding properdin restored this crucial immune function.
Area of Science:
- Immunology
- Microbiology
- Complement System
Background:
- Phagocytosis of Streptococcus pneumoniae by granulocytes is crucial for bacterial clearance.
- The complement system, particularly properdin (P), plays a role in opsonization and phagocytosis.
- Deficiencies in complement components can lead to increased susceptibility to bacterial infections.
Purpose of the Study:
- To investigate the role of properdin (P) in granulocyte phagocytosis of Streptococcus pneumoniae.
- To determine the impact of P deficiency on opsonization and complement component 3 (C3) fixation.
- To elucidate the complement pathway dependency for opsonization of different S. pneumoniae serotypes.
Main Methods:
- Opsonophagocytic assay using P-deficient human serum and S. pneumoniae serotypes.
- Measurement of C3 uptake by S. pneumoniae strains.
- Complement pathway activation assessment using Mg EGTA.
- Heat inactivation of properdin to assess its activity.
Main Results:
- P-deficient serum significantly reduced granulocyte phagocytosis of S. pneumoniae serotypes 6A, 14, 19F, 23F, and 35.
- Opsonization and C3 fixation were defective in P-deficient serum, especially for serotype 23F.
- Addition of native P restored C3 fixation and opsonization, while heat-inactivated P did not.
- Serotype 23F pneumococci showed greater classical pathway dependence for opsonization compared to serotype 35.
Conclusions:
- Properdin is essential for efficient complement-mediated opsonization and phagocytosis of Streptococcus pneumoniae by granulocytes.
- P deficiency primarily affects opsonization rather than intracellular killing.
- Different S. pneumoniae serotypes exhibit varying dependencies on the classical and alternative complement pathways for effective opsonization.