The Teamwork of Neutrophil and Macrophage to Kill Bacterial Pathogens
- Staphylococcus aureus is a common Gram-positive round-shaped bacterium that is a member of the Firmicutes.
- S. aureus is usually part of the human body’s microbiome however, it causes a wide range of illnesses which includes skin infections, food poisoning, and bone/joint infections.
- S. aureus is the primary cause of bacterial endocarditis and the second most frequent agent of bloodstream infections.
- Bacterial endocarditis is a bacterial infection of the inner layer of the heart.
- Immune cells such as neutrophils and macrophages are capable of combating bacterial pathogens.
- Neutrophils and macrophages are important to the innate immune response.
- However, cooperative mechanisms used by neutrophils and macrophages to combat extracellular pathogens are not well understood.
- During infection, neutrophils engulf S. aureus and then initiates bacterial elimination by producing reactive oxygen species or fusing granules containing antimicrobial compounds to the engulfed bacteria.
- Additionally, neutrophils fight extracellular pathogens by producing extracellular “nets” consisting of DNA that can bind and trap pathogens.
- The production of extracellular “nets” by neutrophils is called netosis.
- Researchers discovered that S100A9-deficient neutrophils produce high levels of mitochondrial superoxide in response to S. aureus resulting in the formation of extracellular “nets”.
- Increased suicidal netosis does not improve neutrophil killing of S. aureus in isolation but improves macrophage killing.
- The “net” formation improves antibacterial activity with better engulfment capabilities of macrophages and transferring neutrophil-specific antimicrobial compounds to them.
- Researchers observed similar results in response to other bacterial pathogens such as Streptococcus pneumoniae and Pseudomonas aeruginosa.
- The findings suggest that achieving maximum antibacterial activity through these “net” formations requires macrophages.
- Accelerated and more robust suicidal netosis makes neutrophils proficient at increasing antibacterial activity, especially when A9 deficient.