Host–Pathogen Crosstalk: Molecular Mechanisms, Immune Responses and Therapeutic Opportunities

The immune response is orchestrated by a complex network of molecular and cellular mediators that coordinate host defense against pathogens while maintaining immune homeostasis. Although cytokines and chemokines have traditionally been regarded as the principal regulators of immunity, recent advances in immunology, microbiology, and systems biology have uncovered a diverse array of emerging mediators, including extracellular vesicles, microbial metabolites, lipid mediators, non-coding RNAs, nucleic acids, alarmins, complement components, and immune checkpoint molecules. These mediators play critical roles in regulating innate and adaptive immune responses, inflammation, tissue repair, and host–pathogen interactions. Dysregulation of these signalling networks contributes to the pathogenesis of infectious, inflammatory, autoimmune, metabolic, and malignant diseases. At the same time, many of these molecules have emerged as promising biomarkers and therapeutic targets. A comprehensive understanding of the molecular mechanisms governing immune mediators will facilitate the development of innovative diagnostic tools, targeted immunotherapies, and next-generation vaccines, ultimately advancing precision medicine and improving outcomes across a broad spectrum of human diseases.

The goal of this Research Topic is to provide a multidisciplinary platform for advancing our understanding of the emerging molecular mediators that regulate immune responses in health and disease. We aim to bring together basic, translational, and clinical studies investigating the roles of cytokines, chemokines, extracellular vesicles, microbial metabolites, nucleic acids, lipid mediators, complement components, immune checkpoint molecules, and other signalling mediators in host defense, inflammation, immune homeostasis, and disease pathogenesis. This collection will highlight recent discoveries in the molecular mechanisms underlying immune regulation, identify novel biomarkers and therapeutic targets, and promote innovative approaches for immunomodulation. By fostering collaboration among immunologists, microbiologists, infectious disease specialists, molecular biologists, and clinician-scientists, this Research Topic seeks to accelerate the translation of fundamental discoveries into precision diagnostics, targeted therapies, and next-generation vaccines for infectious, inflammatory, autoimmune, and other immune-mediated diseases.

The immune system relies on a complex network of molecular and cellular mediators that coordinate host defense against microbial pathogens while maintaining immune homeostasis. Although cytokines and chemokines have long been recognized as central regulators of immunity, recent advances in immunology and microbiology have identified numerous additional mediators, such as extracellular vesicles, microbial metabolites, lipid mediators, alarmins, complement components, damage-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs), nucleic acids, non-coding RNAs, immune checkpoint molecules, and metabolic regulators. These mediators influence immune activation, resolution of inflammation, tissue repair, and disease pathogenesis.

Growing evidence demonstrates that these mediators orchestrate the dynamic crosstalk between pathogens and the host immune system, ultimately determining susceptibility to infection, disease severity, pathogen persistence, and clinical outcomes. Therefore, these mediators have emerged as novel biomarkers for disease diagnosis and prognosis, as well as attractive therapeutic targets for next-generation immunomodulatory strategies.

This Research Topic aims to provide an interdisciplinary forum bringing together researchers in microbiology, immunology, infectious diseases and molecular biology to highlight recent advances in the discovery, characterization, and therapeutic exploitation of immune mediators. We welcome studies ranging from fundamental investigations of molecular mechanisms to translational and clinical research evaluating novel diagnostic, prognostic, and therapeutic applications.

Topics of interest include, but are not limited to:

• Novel cytokines, chemokines, growth factors, and soluble immune mediators

• Host–pathogen interactions and immune signalling networks

• Microbial products and metabolites regulating immune responses

• Pattern-recognition receptors, DAMPs, PAMPs, and innate immune sensing

• Extracellular vesicles, exosomes, and intercellular communication

• Non-coding RNAs, microbial nucleic acids, and epigenetic regulation of immunity

• Inflammasomes and inflammatory signalling pathways

• Vaccine-induced immune mediators and correlates of protection

• Multi-omics, systems immunology, artificial intelligence, and computational approaches for identifying novel immune mediators

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Mediators, immunity, molecular mechanisms, PAMPs, PRRs, DAMPs, therapeutcis, vaccines

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.