ROS signaling in innate immunity via oxidative protein modifications Original paper

What was reviewed?

This paper reviewed how reactive oxygen species drive innate immune signaling through oxidative protein modifications. The authors focused on how redox reactions shape immune cell activation, inflammation, and resolution. The review explained how reactive oxygen and nitrogen species act as signaling molecules rather than only toxic byproducts. The authors examined how controlled oxidation modifies proteins, enzymes, and transcription factors during immune responses. They emphasized mechanisms such as cysteine oxidation, protein carbonylation, lipid peroxidation, and nitrosylation. The review framed these processes as central regulators of immune cell metabolism, polarization, and function in both infectious and sterile inflammation.

Who was reviewed?

The review centered on innate immune cells studied across experimental and clinical research, mainly macrophages and neutrophils. The authors synthesized evidence from human cell studies, animal models, and disease contexts such as diabetes, atherosclerosis, neurodegeneration, and inflammatory disorders. They also discussed endothelial cells and other immune populations when relevant to redox signaling. The review did not analyze patient cohorts directly but integrated findings from diverse biological systems to explain conserved immune mechanisms driven by reactive oxygen species in innate immunity.

Most important findings

The review showed that reactive oxygen species regulate innate immunity through precise protein modifications rather than random damage. Hydrogen peroxide acted as a signaling molecule that modified cysteine residues and controlled transcription factors such as NF-κB, NRF2, and HIF-1α. NADPH oxidases and mitochondria served as major sources of reactive oxygen species during immune activation. Macrophages used redox signals to shift between inflammatory and resolving states through metabolic reprogramming. Neutrophils relied on reactive oxygen species for oxidative burst and extracellular trap formation, while excessive oxidation impaired migration and survival. Antioxidant systems such as glutathione and thioredoxin maintained balance and prevented chronic inflammation.

Key implications

This review clarified that targeting redox signaling offers clinical value beyond antioxidant supplementation. Therapeutic strategies can focus on modulating specific redox pathways that control immune cell metabolism, polarization, and inflammatory output. Understanding oxidative protein modifications can improve approaches to chronic inflammatory disease, metabolic disorders, and tissue injury. Clinicians can view reactive oxygen species as regulators of immune function rather than purely harmful agents. Precision redox modulation may support immune resolution while avoiding immune suppression.