A Comprehensive Map of the Monocyte-Derived Dendritic Cell Transcriptional Network Engaged upon Innate Sensing of HIV

Jarrod S. Johnson; Nicholas De Veaux; Alexander W. Rives; Xavier Lahaye; Sasha Y. Lucas; Brieuc P. Perot; Marine Luka; Victor Garcia-Paredes; Lynn M. Amon; Aaron Watters; Ghaith Abdessalem; Alan Aderem; Nicolas Manel; Dan R. Littman; Richard Bonneau; Mickaël M. Ménager

doi:10.1016/j.celrep.2019.12.054

A Comprehensive Map of the Monocyte-Derived Dendritic Cell Transcriptional Network Engaged upon Innate Sensing of HIV

Jarrod S. Johnson, Nicholas De Veaux, Alexander W. Rives, Xavier Lahaye, Sasha Y. Lucas, Brieuc P. Perot, Marine Luka, Victor Garcia-Paredes, Lynn M. Amon, Aaron Watters, Ghaith Abdessalem, Alan Aderem, Nicolas Manel, Dan R. Littman, Richard Bonneau, Mickaël M. Ménager

Research output: Contribution to journal › Article › peer-review

Abstract

Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During HIV-1 infection, human dendritic cells (DCs) can detect the virus through an innate sensing pathway, leading to antiviral interferon and DC maturation. Here, we develop an iterative experimental and computational approach to map the HIV-1 innate response circuitry in monocyte-derived DCs (MDDCs). By integrating genome-wide chromatin accessibility with expression kinetics, we infer a gene regulatory network that links 542 transcription factors with 21,862 target genes. We observe that an interferon response is required, yet insufficient, to drive MDDC maturation and identify PRDM1 and RARA as essential regulators of the interferon response and MDDC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting complexity and cooperativity in the regulatory circuit controlling the response to infection.

Original language	English (US)
Pages (from-to)	914-931.e9
Journal	Cell Reports
Volume	30
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2019.12.054
State	Published - Jan 21 2020

Keywords

ATAC-seq
DNA sensing
IRF3
NF-κB
RNA-seq
STING
cGAS
chromatin modification
innate signaling
network inference

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2019.12.054

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Johnson, J. S., De Veaux, N., Rives, A. W., Lahaye, X., Lucas, S. Y., Perot, B. P., Luka, M., Garcia-Paredes, V., Amon, L. M., Watters, A., Abdessalem, G., Aderem, A., Manel, N., Littman, D. R., Bonneau, R., & Ménager, M. M. (2020). A Comprehensive Map of the Monocyte-Derived Dendritic Cell Transcriptional Network Engaged upon Innate Sensing of HIV. Cell Reports, 30(3), 914-931.e9. https://doi.org/10.1016/j.celrep.2019.12.054

Johnson, JS, De Veaux, N, Rives, AW, Lahaye, X, Lucas, SY, Perot, BP, Luka, M, Garcia-Paredes, V, Amon, LM, Watters, A, Abdessalem, G, Aderem, A, Manel, N, Littman, DR, Bonneau, R & Ménager, MM 2020, 'A Comprehensive Map of the Monocyte-Derived Dendritic Cell Transcriptional Network Engaged upon Innate Sensing of HIV', Cell Reports, vol. 30, no. 3, pp. 914-931.e9. https://doi.org/10.1016/j.celrep.2019.12.054

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abstract = "Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During HIV-1 infection, human dendritic cells (DCs) can detect the virus through an innate sensing pathway, leading to antiviral interferon and DC maturation. Here, we develop an iterative experimental and computational approach to map the HIV-1 innate response circuitry in monocyte-derived DCs (MDDCs). By integrating genome-wide chromatin accessibility with expression kinetics, we infer a gene regulatory network that links 542 transcription factors with 21,862 target genes. We observe that an interferon response is required, yet insufficient, to drive MDDC maturation and identify PRDM1 and RARA as essential regulators of the interferon response and MDDC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting complexity and cooperativity in the regulatory circuit controlling the response to infection.",

keywords = "ATAC-seq, DNA sensing, IRF3, NF-κB, RNA-seq, STING, cGAS, chromatin modification, innate signaling, network inference",

author = "Johnson, {Jarrod S.} and {De Veaux}, Nicholas and Rives, {Alexander W.} and Xavier Lahaye and Lucas, {Sasha Y.} and Perot, {Brieuc P.} and Marine Luka and Victor Garcia-Paredes and Amon, {Lynn M.} and Aaron Watters and Ghaith Abdessalem and Alan Aderem and Nicolas Manel and Littman, {Dan R.} and Richard Bonneau and M{\'e}nager, {Micka{\"e}l M.}",

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doi = "10.1016/j.celrep.2019.12.054",

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AU - Johnson, Jarrod S.

AU - De Veaux, Nicholas

AU - Rives, Alexander W.

AU - Lahaye, Xavier

AU - Lucas, Sasha Y.

AU - Perot, Brieuc P.

AU - Luka, Marine

AU - Garcia-Paredes, Victor

AU - Amon, Lynn M.

AU - Watters, Aaron

AU - Abdessalem, Ghaith

AU - Aderem, Alan

AU - Manel, Nicolas

AU - Littman, Dan R.

AU - Bonneau, Richard

AU - Ménager, Mickaël M.

PY - 2020/1/21

Y1 - 2020/1/21

N2 - Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During HIV-1 infection, human dendritic cells (DCs) can detect the virus through an innate sensing pathway, leading to antiviral interferon and DC maturation. Here, we develop an iterative experimental and computational approach to map the HIV-1 innate response circuitry in monocyte-derived DCs (MDDCs). By integrating genome-wide chromatin accessibility with expression kinetics, we infer a gene regulatory network that links 542 transcription factors with 21,862 target genes. We observe that an interferon response is required, yet insufficient, to drive MDDC maturation and identify PRDM1 and RARA as essential regulators of the interferon response and MDDC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting complexity and cooperativity in the regulatory circuit controlling the response to infection.

AB - Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During HIV-1 infection, human dendritic cells (DCs) can detect the virus through an innate sensing pathway, leading to antiviral interferon and DC maturation. Here, we develop an iterative experimental and computational approach to map the HIV-1 innate response circuitry in monocyte-derived DCs (MDDCs). By integrating genome-wide chromatin accessibility with expression kinetics, we infer a gene regulatory network that links 542 transcription factors with 21,862 target genes. We observe that an interferon response is required, yet insufficient, to drive MDDC maturation and identify PRDM1 and RARA as essential regulators of the interferon response and MDDC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting complexity and cooperativity in the regulatory circuit controlling the response to infection.

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KW - innate signaling

KW - network inference

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A Comprehensive Map of the Monocyte-Derived Dendritic Cell Transcriptional Network Engaged upon Innate Sensing of HIV

Abstract

Keywords

ASJC Scopus subject areas

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