About this Research Topic
The innate immune response, initiated by the recognition of pathogen-, altered cell- or damage-associated molecular patterns by specific soluble or membrane-bound receptors, is responsible for the first-line human defense. The shape of this response hangs in the balance of an ever-growing list of host genetic and epigenetic variants, continually changing to kill the pathogen while maintaining tissue integrity. Rare mutations disrupt this delicate balance, show-casing their effects through severe primary immune deficiencies. While some of these greatly reduce life expectations by exacerbating inflammatory reactions, others are conditional to pathogenic challenges, as is the case for mendelian susceptibility to mycobacterial infections. Those rather subtle consequences of common polymorphisms melt within this big picture and are often overlooked, mainly if confined to regulatory-regions, in poorly investigated topologically-associated chromatin domains. Nevertheless, they often simultaneously appear as potential disease modifiers in outnumbered genetic association studies and as expression, sometimes splicing quantitative-trait loci, possibly modifying gene expression. High-throughput technologies made it possible to follow-up these effects, even in a single cell, allowing the description of over-time modifying epigenetic and transcriptional landscapes during disease.
Using the approaches mentioned above, it may soon appear that the consequences of polymorphisms in primary and secondary-response innate immunity genes may differ from each other. Most of the first present CpG islands are promptly activated by post-translational modifications of transcription factors. In contrast, second-response genes require newly synthesized regulatory proteins due to activation of primary response genes, as well as ATP-driven chromatin remodeling. Their evolutionary constraints may also differ according to specific environmental circumstances imposed on different human populations. We hope to answer these questions now, after two decades since the announcement of the first draft of the Human Genome.
Our Research Topic centers on investigating the human genome, epigenome, and regulome diversity, and their impact on shaping the innate immune response. Areas covered include, but are not limited to: large scale sequence analysis; epigenomics; functional genomics; population genetics and evolution; comparative biology; proteomics; systems and network biology; genomics of disease and clinical genomics; bioinformatics. Genome-wide and large-scale targeted association studies are welcome, and well-designed functional validation of association studies of innate immunity genes.
We welcome the submission of Original Research, Review, Mini Review, Perspective, and Methods articles, with a particular interest in the following topics:
1. The human genome, epigenome, and regulome diversity modulating the susceptibility to diseases
2. Phenotypic or pleiotropic effects of genetic and epigenetic variation in innate immunity genes on the susceptibility to diseases.
3. Evolution and population genetics studies involving genes of the innate immune system.
4. Microbiome and its interaction with innate immune function and human evolution.
5. The evolutionary race between host and pathogen (Red Queen hypothesis) shaping genetic and epigenetic variants of genes of innate immune responses in human populations.
6. Large scale laboratory or bioinformatics methods for screening and detecting genomic variants with functional relevance and evolutionary analysis methods.
7. The double-edged sword effect of polymorphisms associated with innate immunity.
8. Clinical and personalized medicine application of genetic, epigenetic, and regulome variants that affect innate immune responses.
9. Transgenerational epigenetic effects on the quality of the innate immune response.
10. Modifiers of the epitranscriptome (epigenetic modifications on RNA molecules) and their effects on the innate immune response.
Using the approaches mentioned above, it may soon appear that the consequences of polymorphisms in primary and secondary-response innate immunity genes may differ from each other. Most of the first present CpG islands are promptly activated by post-translational modifications of transcription factors. In contrast, second-response genes require newly synthesized regulatory proteins due to activation of primary response genes, as well as ATP-driven chromatin remodeling. Their evolutionary constraints may also differ according to specific environmental circumstances imposed on different human populations. We hope to answer these questions now, after two decades since the announcement of the first draft of the Human Genome.
Our Research Topic centers on investigating the human genome, epigenome, and regulome diversity, and their impact on shaping the innate immune response. Areas covered include, but are not limited to: large scale sequence analysis; epigenomics; functional genomics; population genetics and evolution; comparative biology; proteomics; systems and network biology; genomics of disease and clinical genomics; bioinformatics. Genome-wide and large-scale targeted association studies are welcome, and well-designed functional validation of association studies of innate immunity genes.
We welcome the submission of Original Research, Review, Mini Review, Perspective, and Methods articles, with a particular interest in the following topics:
1. The human genome, epigenome, and regulome diversity modulating the susceptibility to diseases
2. Phenotypic or pleiotropic effects of genetic and epigenetic variation in innate immunity genes on the susceptibility to diseases.
3. Evolution and population genetics studies involving genes of the innate immune system.
4. Microbiome and its interaction with innate immune function and human evolution.
5. The evolutionary race between host and pathogen (Red Queen hypothesis) shaping genetic and epigenetic variants of genes of innate immune responses in human populations.
6. Large scale laboratory or bioinformatics methods for screening and detecting genomic variants with functional relevance and evolutionary analysis methods.
7. The double-edged sword effect of polymorphisms associated with innate immunity.
8. Clinical and personalized medicine application of genetic, epigenetic, and regulome variants that affect innate immune responses.
9. Transgenerational epigenetic effects on the quality of the innate immune response.
10. Modifiers of the epitranscriptome (epigenetic modifications on RNA molecules) and their effects on the innate immune response.
Keywords: innate immunity, epigenetics, transcriptome, ncRNA, evolution, infection, polymorphisms, mutation, PAMPs, ACAMPs, DAMPs, PRRs, pattern-recognition receptors, pathogen-associated molecular patterns, phagocytic receptors, complement system, TLR, toll-like receptors, CLR, C-type lectin receptors, inflammasome, NOD-like receptors, NLR, RIG-I-like receptors, RLR, KIR, natural killer receptors
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