Adenosine Triphosphate Neutralizes Pneumolysin-Induced Neutrophil Activation

Area of Science:

• Immunology
• Microbiology

Background:

• Extracellular adenosine triphosphate (ATP) plays a role in purinergic chemotaxis during tissue infections.
• Neutrophils are crucial for bacterial clearance but can cause tissue damage through excessive activation in pneumococcal infections.
• The interplay between ATP and neutrophil responses in pneumococcal infections requires further investigation.

Purpose of the Study:

• To investigate the role of extracellular ATP in modulating neutrophil activation in response to pneumococcal infections.
• To determine how pneumolysin, a key pneumococcal virulence factor, influences neutrophil activation and whether ATP can counteract this effect.

Main Methods:

• Primary human neutrophils were stimulated with Streptococcus pneumoniae (TIGR4 strain) and its pneumolysin-deficient mutant.
• Neutrophil activation was assessed by measuring secreted resistin and secretome profiling via mass spectrometry.
• The direct effect of recombinant pneumolysin and varying concentrations of ATP on neutrophil activation was evaluated.

Main Results:

• Pneumococci potently induce neutrophil degranulation, with pneumolysin identified as a major trigger.
• Pneumolysin-induced neutrophil activation is partially independent of bacterial lysis and is inhibited by extracellular ATP.
• Proteomic analysis confirmed that ATP significantly reduces pneumolysin-mediated neutrophil activation.

Conclusions:

• Pneumolysin acts as a potent neutrophil activator, despite its cytolytic properties.
• Extracellular ATP effectively mitigates pneumolysin-induced neutrophil activation, suggesting a protective role in controlling inflammation.
• Understanding this interaction could lead to novel therapeutic strategies for pneumococcal infections.