Infectious diseases persist as a major global public health threat, with the emergence of novel pathogens and antimicrobial resistance presenting formidable challenges to modern medicine. Within this context, natural medicines and complex formulations derived from traditional medical systems (e.g., Traditional Chinese Medicine, Ayurveda, African Traditional Medicine) constitute valuable resources for anti-infective drug development due to their polypharmacological profiles and low propensity for inducing resistance. Nevertheless, the core therapeutic value of these interventions—precisely modulating the host immune system to eliminate pathogens, suppress cytokine storms, and promote tissue repair—requires systematic elucidation through contemporary immunological methodologies.

Advances in immunology—particularly in innate immune recognition, adaptive immune regulation, immunometabolism, mucosal immunity, host-microbiota interactions, programmed cell death pathways (e.g., pyroptosis, ferroptosis), and tissue-repair immunity—provide unprecedented mechanistic frameworks to deconvolve the immunomodulatory "black box" of traditional therapeutics. Rigorous investigation into how these agents: (i) Modulate functional states of immune cells (including macrophages, neutrophils, T/B lymphocytes, NK cells, and ILCs), (ii) Target signaling pathways (e.g., TLR, NLR, RLR, cGAS–STING, inflammasomes, JAK–STAT), (iii) Remodel immune microenvironments, and (iv) Reprogram immunometabolic networks, is essential for validating their scientific merit and advancing translational applications.

This Research Topic aims to decipher the immunomodulatory mechanisms by which natural medicines and traditional formulations combat infections. We seek to integrate cutting-edge immunology concepts (e.g., immunometabolism, novel cell death pathways, tissue-resident immunity) and advanced methodologies (multi-omics, AI, organoid models) to elucidate how these agents precisely regulate host defenses. Furthermore, we will foster translational innovation through rigorous evaluation frameworks, synergistic target deconvolution, and development of novel delivery systems. Ultimately, this collection will bridge traditional wisdom with modern science to advance evidence-based validation of natural therapeutics as next-generation anti-infective and immunoregulatory strategies.

This Research Topic welcomes investigations on traditional complex formulations, botanical extracts, and isolated phytochemicals, with emphasis on:

(1)Immunomodulatory mechanisms regulating: Immune cell dynamics (macrophages/T/B cells/ILCs) and signaling pathways (TLR/NLR/inflammasome/cGAS-STING), Immunometabolic reprogramming in infection microenvironments

(2)Host-microbiota crosstalk interventions (e.g., gut-immune axis modulation)

(3)Emerging targeting strategies for:Ferroptosis regulation, Tissue-resident T cell programming, Immune epigenetic remodeling

(4)Synergistic networks of multi-component botanical therapeutics

(5)Advanced delivery systems (nano/exosome/liposomal) enhancing bioavailability and targeted immunomodulation of phytochemicals

(6)Translational development of:Natural adjuvant platforms, Plant-derived host-directed therapies (HDTs)

Excluded:

Studies lacking mechanistic immunology data;

Non-infection contexts (e.g., cancer/autoimmunity);

Isolated phytochemical analyses without immune functional validation.

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Decoding Traditional Wisdom: Mechanisms and Transformations of Natural Medicines Regulating Anti-infectious Immunity