Natural compounds as modulators of neutrophil activation: from bench to therapeutic promise

Neutrophils are the most abundant leukocytes in human blood and constitute the first line of defense against pathogens. Their activation, leading to phagocytosis, degranulation, and the release of Neutrophil Extracellular Traps (NETs), is crucial for innate immunity. However, dysregulated or excessive neutrophil activation is a hallmark of numerous chronic inflammatory and autoimmune diseases, such as rheumatoid arthritis, sepsis, acute lung injury, and atherosclerosis. Current strategies to control hyperactive neutrophils often lack specificity and can lead to immunosuppression. In this context, natural compounds (derived from plants, marine organisms, or microorganisms) represent a vast and largely untapped reservoir of bioactive molecules. These compounds offer exceptional chemical diversity and have historically been a prolific source of pharmacologically active agents, presenting a promising avenue for the discovery of novel, targeted immunomodulators with potentially fewer side effects.The primary goal of this Research Topic is to collate cutting-edge research that elucidates the mechanisms by which natural molecules modulate neutrophil functions, including recruitment, activation, oxidative burst, NETosis, and apoptosis. While the therapeutic potential of many natural products is acknowledged, a systematic understanding of their direct molecular targets and signaling pathways in neutrophils is often lacking. This collection aims to bridge this gap by fostering interdisciplinary studies that combine phytochemistry, pharmacology, and immunology. We seek to highlight recent advances in the identification and characterization of novel natural compounds, the repurposing of known molecules, and the development of natural product-inspired synthetic analogs with an immunological perspective.Ultimately, this topic will provide a comprehensive platform to explore how these molecules can be harnessed to fine-tune neutrophil responses, thereby paving the way for the development of next-generation therapeutics for inflammation-driven pathologies. We welcome contributions that move beyond descriptive findings to offer mechanistic insights and validate efficacy in robust in vivo models on immune system disorders.This Research Topic will define the current landscape and future directions of natural product research in neutrophil biology and its immunomodulatory properties. We aim to cover the entire spectrum, from the discovery of novel bioactive compounds to the detailed dissection of their anti-inflammatory mechanisms. We welcome the submission of Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:• Discovery and Characterization: Screening of plant, marine, or microbial extracts for neutrophil-modulating activities.• Mechanistic Insights: Elucidation of signaling pathways (e.g., MAPK, PI3K/Akt, NF-κB) and molecular targets affected by natural compounds and involved on immune modulation.• NETosis Regulation: The role of natural products in inducing or inhibiting the formation of Neutrophil Extracellular Traps (NETs).• Inflammation Resolution: Contributions to promoting neutrophil apoptosis and efferocytosis.• Preclinical and Clinical Studies: Efficacy evaluation of natural compounds in models of sterile inflammation, infection, and autoimmunity.• Drug Delivery and Formulation: Novel approaches to enhance the bioavailability and efficacy of natural immunomodulators. Topic editors: Riadh Ben Mansour, Zhengping Huang, Nesrine ELLOUMI Source: https://www.frontiersin.org/research-topics/75858/natural-compounds-as-modulators-of-neutrophil-activation-from-bench-to-therapeutic-promise