PUBLICATION
Animal Models for the Study of Nucleic Acid Immunity: Novel Tools and New Perspectives
- Authors
- Vila, I.K., Fretaud, M., Vlachakis, D., Laguette, N., Langevin, C.
- ID
- ZDB-PUB-200830-12
- Date
- 2020
- Source
- Journal of molecular biology 432(20): 5529-5543 (Review)
- Registered Authors
- Fretaud, Maxence
- Keywords
- Drug screening, Inflammatory models, Innate immunity, Interferon signaling, STING
- MeSH Terms
-
- Animals
- Antiviral Agents/pharmacology
- Cytosol/metabolism
- DNA, Viral/analysis
- Drug Evaluation, Preclinical
- Evolution, Molecular
- High-Throughput Screening Assays/methods
- Immunity*
- Immunity, Innate
- Inflammation/immunology
- Inflammation/metabolism
- Interferon Type I/metabolism
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Mice
- Models, Animal*
- Mutation
- Nucleic Acids/immunology*
- Nucleotidyltransferases/genetics
- Nucleotidyltransferases/metabolism
- Signal Transduction
- PubMed
- 32860771 Full text @ J. Mol. Biol.
Citation
Vila, I.K., Fretaud, M., Vlachakis, D., Laguette, N., Langevin, C. (2020) Animal Models for the Study of Nucleic Acid Immunity: Novel Tools and New Perspectives. Journal of molecular biology. 432(20):5529-5543.
Abstract
Unresolved inflammation fosters and supports a wide range of human pathologies. There is growing evidence for a role played by cytosolic nucleic acids in initiating and supporting pathological chronic inflammation. In particular, the cGAS-STING pathway has emerged as central to the mounting of nucleic acid-dependent type I interferon (IFN) responses, leading to the identification of small molecule modulators of STING that have raised clinical interest. However, several new challenges have emerged, representing potential obstacles to efficient clinical translation. Indeed, the current literature underscores that nucleic acid-induced inflammatory responses are subjected to several layers of regulation, further suggesting complex coordination at the cell-type, tissue or organism level. Untangling the underlying processes is paramount to the identification of specific therapeutic strategies targeting deleterious inflammation. Herein, we present an overview of human pathologies presenting with deregulated IFN levels and with accumulation of cytosolic nucleic acids. We focus on the central role of the STING adaptor protein in these pathologies and discuss how in vivo models have forged our current understanding of nucleic acid immunity. We present our opinion on the advantages and limitations of zebrafish and mice models to highlight their complementarity for the study of inflammatory human pathologies and the development of therapeutics. Finally, we discuss high throughput screening strategies that generate multi-parametric datasets that allow integrative analysis of heterogeneous information (imaging and omics approaches). These approaches are likely to structure the future of screening strategies for the treatment of human pathologies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping