NSAIDs Beyond COX in Infection: Innate Sensing, Resolution, and Biofilm vs Planktonic Outcomes

Non-steroidal anti-inflammatory drugs (NSAIDs) are classically defined by cyclooxygenase (COX) inhibition, yet increasing evidence shows that many NSAIDs also reshape host responses through COX-independent mechanisms that intersect with innate immune sensing and inflammatory programming. These effects can influence PRR-linked signaling, inflammasome activity, leukocyte trafficking and effector functions, and the balance between tissue-damaging inflammation and pro-resolving pathways. In infection, that balance is decisive and context dependent: the same NSAID exposure may reduce immunopathology in one setting but impair pathogen control in another, depending on timing, dose, tissue, pathogen traits, and host factors.This Research Topic will feature mechanistic, translational, and clinical studies that clarify when NSAIDs can be repurposed—or strategically avoided—to modulate infection outcomes. We particularly welcome work connecting NSAID immunomodulation to innate immune pathways (e.g., TLR and NOD-like receptor signaling, IL-1 family dynamics, pyroptosis), myeloid cell function (neutrophil chemotaxis, NET formation, phagocytosis and oxidative burst; macrophage activation states and immunometabolism), and resolution biology (efferocytosis, lipid mediator class switching, and repair programs). Studies integrating pharmacology with host–pathogen interactions, including omics, imaging, and in vivo models, are encouraged.A key emphasis is microbial lifestyle. Biofilm-associated infections establish distinct immune-evasion strategies and inflammatory “set points” compared with planktonic growth, which may alter how NSAID-driven immune tuning affects persistence, antimicrobial tolerance, and outcomes such as resolution versus chronicity. We invite submissions spanning bacterial, fungal, and viral systems and across tissues (e.g., lung, gut, skin, urinary tract, oral cavity), including evidence on NSAID interactions with antibiotics/antifungals (synergy, antagonism, tolerance/persistence) and clinical studies that support biomarker development and risk stratification for NSAID use during infection.We welcome articles addressing, but not limited to, the following themes:-COX-independent NSAID actions on PRR pathways (e.g., TLRs, NOD-like receptors) and downstream transcriptional programs-NSAID effects on inflammasome activation, pyroptosis, and IL-1 family cytokine dynamics-Modulation of neutrophil functions (chemotaxis, NETs, phagocytosis, oxidative burst) in acute vs chronic infection-Macrophage polarization and metabolic reprogramming (glycolysis/OXPHOS) shaped by specific NSAIDs-Impact on pro-resolving mediators and resolution circuits (efferocytosis, lipid mediator class switching)-Differences in host responses to planktonic versus biofilm infections under NSAID exposure (timing, dose, tissue)-NSAID influences on biofilm formation, dispersal, quorum sensing, and extracellular matrix composition (direct or host-mediated)-Interactions with antibiotics/antifungals: synergy, antagonism, and effects on tolerance/persistence-Tissue-specific outcomes (lung, gut, skin, urinary tract, oral cavity) and implications for immunopathology vs clearance-Translational and clinical evidence: observational studies, trials, biomarkers, and risk stratification for NSAID use during infection Topic editors: Diana Camelia Nuta, Carmen Limban, Roberta Rocca Source: https://www.frontiersin.org/research-topics/78252/nsaids-beyond-cox-in-infection-innate-sensing-resolution-and-biofilm-vs-planktonic-outcomes