Streptococcal pyrogenic exotoxin B inhibits apoptotic cell clearance by macrophages through protein S cleavage

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Efficient clearance of apoptotic cells by macrophages is crucial for tissue homeostasis.
• Group A Streptococcus (GAS) infection involves streptococcal pyrogenic exotoxin B (SPE B), which was previously shown to reduce phagocytic activity.

Purpose of the Study:

• To investigate the inhibitory effect of SPE B on protein S-mediated phagocytosis of apoptotic cells.
• To elucidate the mechanism by which SPE B interferes with apoptotic cell clearance.

Main Methods:

• Assessing phagocytosis of apoptotic cells in the presence of SPE B and protein S.
• Evaluating the binding of protein S to apoptotic cells after SPE B treatment.
• Analyzing the cleavage of protein S by SPE B in vitro and in vivo.
• Comparing the effects of wild-type GAS and speB mutant strains.

Main Results:

• SPE B significantly inhibited both serum- and purified protein S-mediated phagocytosis of apoptotic cells.
• SPE B treatment reduced the binding ability of protein S to apoptotic cells.
• Bacterial supernatants from GAS NZ131, but not the speB mutant, reduced protein S binding.
• SPE B directly cleaved protein S in vitro and in vivo, leading to disrupted phagocytosis and loss of C4b-binding protein association.

Conclusions:

• SPE B degrades protein S, thereby inhibiting the clearance of apoptotic cells by macrophages.
• This represents a novel pathogenic mechanism for SPE B in GAS infections.
• Disruption of apoptotic cell clearance by SPE B contributes to pathogenesis.