Innate Immune Signaling Proteins and Complexes: Genetic Regulation and Molecular Mechanisms

Innate immunity provides rapid host defense against infection and tissue damage in a time-sensitive manner. The immune response to pathogens or danger-associated signals is governed by complex and tightly regulated molecular networks composed of germline-encoded sensors and downstream signaling molecules. Detection of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), RIG-I–like receptors (RLRs), cyclic GMP–AMP synthase (cGAS), and inflammasomes initiates signaling cascades involving kinases, ubiquitin ligases, and adaptor proteins. Several of these proteins assemble into supramolecular complexes to enable efficient signal transduction and amplification. The coordinated activation of these pathways triggers innate immune responses, such as the production of interferons, pro-inflammatory cytokines, and chemokines, which in turn recruit specialized immune cells to the site of infection, facilitating the clearance of pathogens or damaged cells. Dysregulation of innate immune signaling can lead to chronic inflammation and contribute to the development of autoimmune and inflammatory diseases.Innate immune signaling is controlled at multiple levels, from gene regulation and sequence variation to protein conformational dynamics, post-translational modifications, and higher-order assembly. Epigenetic modulations, mutations, and polymorphisms in innate immune signaling proteins are now recognized as key drivers of autoinflammatory, autoimmune, infectious, and even cancer-related pathologies. Understanding how genetic regulation shapes the structure, activity, and interactions of innate immune signaling proteins and complexes is therefore essential for uncovering disease mechanisms and identifying new therapeutic targets. These insights create opportunities for improved diagnostics, risk stratification, and precision therapeutic development in both common and rare diseases.This research topic focuses on the molecular and genetic principles that govern innate immune signaling. We welcome recent advances and research spanning diverse innate immune pathways, including pattern recognition receptors, nucleic acid sensors, inflammasomes, and downstream signaling networks that regulate cytokine production and inflammatory gene expression, with an emphasis on studies that link genetic and genomic variation to mechanisms using experimental or computational approaches.Areas of interest include, but are not limited to:• The impact of genetic variation.• Post-translational modifications and protein conformational changes.• Oligomerization and phase transitions.• Systems-level regulatory mechanisms.• Translational studies that inform therapeutic target identification or preclinical development. Topic editors: Meenakshi Sharma, Liwu Li Source: https://www.frontiersin.org/research-topics/78374/innate-immune-signaling-proteins-and-complexes-genetic-regulation-and-molecular-mechanisms