Innate immunity is a foundational field in immunology, critical for understanding how organisms sense and respond to danger, be it pathogens or sterile inflammatory triggers, through complex and highly conserved molecular mechanisms. Recent years have seen significant advances in elucidating how pattern recognition receptors (PRRs), particularly Toll-like receptors (TLRs), govern the immediate and adaptive aspects of immune responses. While considerable progress has been made in identifying PRR ligands and downstream signaling pathways, fundamental questions persist regarding the integration of these pathways with soluble mediators such as natural antibodies, complement systems, and defensins, as well as the precise mechanisms governing balance between protective immunity and pathological inflammation. Notably, the emergence of the trained immunity paradigm, where innate immune cells adopt long-term functional changes, has added complexity to our understanding of innate immune regulation and opened new avenues in both basic and translational research.
The overarching aim of this Research Topic is to deepen our mechanistic insight into how innate immune receptors, signaling networks, and soluble mediators interact to detect, interpret, and respond to infectious as well as endogenous threats. Central questions include how PRR- and TLR-mediated signaling orchestrates the differentiation and functional adaptation of innate immune cells, how molecular adjuvants can be leveraged to modulate these responses, and how such processes shape or disrupt tissue homeostasis in both health and disease. Emphasis will also be placed on research that explores trained immunity, with a focus on the epigenetic and metabolic reprogramming events driving innate memory, as well as on studies investigating the consequences of innate immune modulation for systemic inflammatory diseases, autoimmunity, and organ-specific pathologies.
This Research Topic is defined by its focus on molecular and cellular pathways underpinning innate immune recognition, response, and adaptation across multiple physiological and pathological contexts. Studies with a translational perspective that link fundamental discoveries to immunomodulatory interventions are especially encouraged. To gather further insights into the molecular boundaries and functional implications of innate immunity, we welcome articles addressing, but not limited to, the following themes:
• Mechanisms and diversity of pattern recognition receptors, including TLRs, in health and disease • Crosstalk between PRRs, signaling networks, and soluble mediators (e.g., complement, defensins, natural antibodies) • Molecular adjuvants and their role in fine-tuning innate immune responses and trained immunity • Epigenetic and metabolic reprogramming in innate immune cell memory and immunomodulation • Innate immune contributions to tissue homeostasis, maladaptation, and disease pathogenesis (e.g., inflammation, autoimmunity, fibrosis) • Translational strategies for immunomodulation targeting molecular innate immune pathways
We welcome original research articles, comprehensive reviews, and perspective pieces that provide mechanistic insights into innate immune recognition, signaling, and adaptation. Manuscripts may explore pattern recognition receptors (PRRs), Toll-like receptors (TLRs), soluble mediators, trained immunity, epigenetic and metabolic reprogramming, molecular adjuvants, and translational immunomodulatory strategies. Submissions should ideally combine experimental, computational, or translational approaches and link fundamental discoveries to broader implications for tissue homeostasis, inflammation, autoimmunity, or disease pathogenesis. Studies offering novel insights, innovative methodologies, or forward-looking perspectives that advance the field of innate immunity are particularly encouraged.
The topic editors declare no conflict of interest
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
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Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
