Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was reviewed?
This review examined how neutrophils generate reactive oxygen species through NADPH oxidase activation and how bacterial pathogens resist this oxidative defense. The authors synthesized molecular and cellular research that explains how surface receptors on neutrophils trigger oxidase assembly, how reactive oxygen species act as antimicrobial tools, and how dysregulation causes disease. The paper focused on signaling pathways, protein phosphorylation, and receptor-mediated activation that control oxidative burst strength and location during infection.
Who was reviewed?
The review drew from experimental work involving human neutrophils, murine neutrophils, and clinical observations from patients with chronic granulomatous disease. It also integrated studies on bacterial pathogens that commonly infect immunocompromised hosts, including Staphylococcus aureus, Salmonella species, Aspergillus, and Candida albicans. These organisms served as key models to understand host–pathogen interactions under oxidative stress conditions.
Most important findings
The authors showed that neutrophils rely on tightly regulated NADPH oxidase activation to generate reactive oxygen species that kill invading bacteria while limiting tissue damage. They highlighted how receptors such as Fc receptors, integrins, G-protein–coupled receptors, and Toll-like receptors coordinate intracellular signaling to assemble the oxidase complex. The review also showed that many bacterial pathogens counter this defense by blocking oxidase assembly, neutralizing reactive oxygen species, or repairing oxidative damage. These resistance strategies explain why certain pathogens dominate infections in patients with impaired oxidative burst, especially in chronic granulomatous disease.
Key implications
This review clarifies why balanced reactive oxygen species production determines both effective immunity and inflammatory pathology. It shows that failures in NADPH oxidase signaling increase susceptibility to specific bacterial and fungal infections, while excessive activation drives tissue injury and autoimmune disease. Clinicians can use this framework to interpret immune defects better, predict infection risk, and understand why therapies that alter neutrophil activation may shift host defense outcomes. The paper also supports targeting oxidase regulation rather than complete inhibition to preserve antimicrobial function.