Streptococcus pyogenes M1T1 Variants Induce an Inflammatory Neutrophil Phenotype Including Activation of Inflammatory...

Area of Science:

• Microbiology
• Immunology
• Pathogenesis

Background:

• Invasive group A Streptococcus (GAS) infections are characterized by rapid tissue damage and uncontrolled inflammation.
• Neutrophils are critical immune cells responding to GAS, but their precise role in invasive disease is complex.
• Understanding neutrophil interactions with different GAS strains is key to explaining disease severity.

Purpose of the Study:

• To investigate and compare the neutrophil response to two distinct group A Streptococcus M1T1 isolates: strain 5448 and its animal-passaged variant 5448AP.
• To elucidate how these GAS strains influence neutrophil function, including proliferation, reactive oxygen species (ROS) production, cell death, and inflammatory caspase activation.

Main Methods:

• Co-incubation of human neutrophils with GAS strains 5448 and 5448AP.
• Measurement of GAS proliferation and neutrophil reactive oxygen species (ROS) production.
• Assessment of neutrophil apoptosis and expression of inflammatory caspases (caspase-1 and caspase-4) in vitro and in vivo.

Main Results:

• Strain 5448AP promoted GAS proliferation and reduced neutrophil ROS production compared to strain 5448.
• Both strains induced neutrophil death, but 5448AP significantly reduced apoptosis.
• Both GAS strains activated inflammatory caspases (caspase-1 and caspase-4) in neutrophils, detected both in vitro and in vivo.

Conclusions:

• GAS strain 5448AP induces an inflammatory neutrophil phenotype characterized by reduced ROS production and impaired apoptosis.
• This altered neutrophil response may lead to ineffective bacterial eradication and heightened inflammation.
• The findings suggest that specific GAS strain characteristics, like those of 5448AP, contribute to the severity of invasive GAS infections.