NDLI: Dynamic Cross Talk Model of the Epithelial Innate Immune Response to Double-Stranded RNA Stimulation: Coordinated Dynamics Emerging from Cell-Level Noise

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Dynamic Cross Talk Model of the Epithelial Innate Immune Response to Double-Stranded RNA Stimulation: Coordinated Dynamics Emerging from Cell-Level Noise

Content Provider	PubMed Central
Author	Roberto, Bertolusso Tian, Bing Zhao, Yingxin Vergara, Leoncio Sabree, Aqeeb Marta, Iwanaszko Tomasz, Lipniacki Brasier, Allan R. Kimmel, Marek
Editor	Meurs, Eliane F.
Copyright Year	2014
Abstract	We present an integrated dynamical cross-talk model of the epithelial innate immune reponse (IIR) incorporating RIG-I and TLR3 as the two major pattern recognition receptors (PRR) converging on the RelA and IRF3 transcriptional effectors. bioPN simulations reproduce biologically relevant gene-and protein abundance measurements in response to time course, gene silencing and dose-response perturbations both at the population and single cell level. Our computational predictions suggest that RelA and IRF3 are under auto- and cross-regulation. We predict, and confirm experimentally, that RIG-I mRNA expression is controlled by IRF7. We also predict the existence of a TLR3-dependent, IRF3-independent transcription factor (or factors) that control(s) expression of MAVS, IRF3 and members of the IKK family. Our model confirms the observed dsRNA dose-dependence of oscillatory patterns in single cells, with periods of 1–3 hr. Model fitting to time series, matched by knockdown data suggests that the NF-κB module operates in a different regime (with different coefficient values) than in the TNFα-stimulation experiments. In future studies, this model will serve as a foundation for identification of virus-encoded IIR antagonists and examination of stochastic effects of viral replication.
Related Links	http://dx.doi.org/10.1371/journal.pone.0093396
Starting Page	93396
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	9
Language	English
Publisher	Public Library of Science
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Correction: Dynamic Cross Talk Model of the Epithelial Innate Immune Response to Double-Stranded RNA Stimulation: Coordinated Dynamics Emerging from Cell-Level Noise

HIV protease inhibitors alter innate immune response signaling to double-stranded RNA in oral epithelial cells: implications for immune reconstitution inflammatory syndrome?

Limited specificity of IRF3 and ISGF3 in the transcriptional innate-immune response to double-stranded RNA

Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis

Response of airway epithelial cells to double-stranded RNA in an allergic environment

Influenza A virus circumvents the innate immune response through the sequestration of double-stranded RNA

Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis

Response of airway epithelial cells to double-stranded RNA in an allergic environment

SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial derived cells and cardiomyocytes

Dynamic Cross Talk Model of the Epithelial Innate Immune Response to Double-Stranded RNA Stimulation: Coordinated Dynamics Emerging from Cell-Level Noise

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Correction: Dynamic Cross Talk Model of the Epithelial Innate Immune Response to Double-Stranded RNA Stimulation: Coordinated Dynamics Emerging from Cell-Level Noise

HIV protease inhibitors alter innate immune response signaling to double-stranded RNA in oral epithelial cells: implications for immune reconstitution inflammatory syndrome?

Limited specificity of IRF3 and ISGF3 in the transcriptional innate-immune response to double-stranded RNA

Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis

Response of airway epithelial cells to double-stranded RNA in an allergic environment

Influenza A virus circumvents the innate immune response through the sequestration of double-stranded RNA

Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis

Response of airway epithelial cells to double-stranded RNA in an allergic environment

SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial derived cells and cardiomyocytes

Dynamic Cross Talk Model of the Epithelial Innate Immune Response to Double-Stranded RNA Stimulation: Coordinated Dynamics Emerging from Cell-Level Noise