Does our immune system produce hydrogen peroxide to kill bacteria?

The Human Immune System Produces Hydrogen Peroxide to Kill Bacteria

Yes, the human immune system produces hydrogen peroxide (H₂O₂) as a critical component in bacterial killing mechanisms, particularly through neutrophils and antibodies during the oxidative burst process. 1, 2

Mechanisms of Hydrogen Peroxide Production in Immune Defense

Neutrophil-Mediated Bacterial Killing

• Polymorphonuclear leukocytes (PMNs or neutrophils) generate H₂O₂ through the respiratory burst process:
  • Oxygen is consumed and converted to superoxide (O₂⁻)
  • Superoxide is then converted to H₂O₂ 2
  • H₂O₂ is deposited within phagocytic vacuoles near ingested bacteria

Antibody-Catalyzed H₂O₂ Production

• Antibodies can catalyze the generation of H₂O₂ from singlet molecular oxygen and water
• This process contributes to bacterial killing regardless of the antibody's antigen specificity 1

Hydrogen Peroxide's Role in Bacterial Destruction

H₂O₂ serves as a precursor for multiple bactericidal mechanisms:

1. Myeloperoxidase (MPO) System:

   • H₂O₂ reacts with MPO and halides to form hypochlorous acid (HOCl)
   • This creates potent antimicrobial compounds 2

2. Hydroxyl Radical Formation:

   • H₂O₂ can react with superoxide and/or iron to form highly toxic hydroxyl radicals (·OH)
   • These radicals cause significant damage to bacterial structures 2

3. Ozone-Like Oxidants:

   • Recent evidence suggests antibodies catalyze water-oxidation pathways that produce an ozone-like oxidant
   • This oxidant is generated during neutrophil activation and inflammation 1

Clinical Evidence Supporting H₂O₂'s Importance

The critical role of H₂O₂ in immune defense is demonstrated by:

• Chronic Granulomatous Disease (CGD): Patients with CGD have neutrophils that cannot effectively generate H₂O₂

  • These patients show impaired ability to kill catalase-positive bacteria
  • They suffer from recurrent infections 2

• Deficiencies in related systems: Patients with myeloperoxidase or lactoferrin deficiencies also show increased susceptibility to infections 2

Bacterial Countermeasures Against H₂O₂

Interestingly, some bacteria have evolved to produce their own H₂O₂ as a counter-defense mechanism:

• Streptococcus pneumoniae releases H₂O₂ that can inhibit inflammasomes (key components of innate immunity)
• This contributes to bacterial colonization by suppressing host immune responses 3
• Similarly, oral commensal bacteria like Streptococcus oralis can block inflammasome activation through H₂O₂ production 3

Bacterial Adaptation to Oxidative Stress

When exposed to sublethal concentrations of H₂O₂, bacteria like E. coli respond with:

• Activation of specific antioxidant responses (OxyR-mediated)
• Upregulation of catalase-encoding genes (katG) that degrade extracellular H₂O₂
• Coordinated upregulation of cysteine biosynthesis pathways to replenish oxidized cysteine and glutathione stores 4

In summary, hydrogen peroxide production represents a fundamental antimicrobial mechanism in the human immune system, though certain pathogens have evolved sophisticated countermeasures to this defense strategy.