The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation

Langlais, David; Barreiro, Luis B.; Gros, Philippe

doi:10.1083/jcb.2127oia59

Cited by 33 publications

(49 citation statements)

References 20 publications

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“…Specifically, IRF1 and STAT1 were shown to bind to the cis-regulatory region of iNOS. The NO production of macrophages was completely abrogated in irf1 −/− mouse 25 . In the current study, IRF1, STAT1 and SPI1 (gene that encodes PU.1) were differentially expressed at the 3 hours time point.…”

Section: Discussionmentioning

confidence: 92%

“…1). Transcription factors are known to be the master regulators of macrophage functions 24,25 . After applying a filter to only include transcription factors 11 Transcription Factors (TFs) (STAT1, IRF7, SPI1, STAT4, IRF1, HIF1A, FOXO3, REL, NFAT5, HIC1, and IRF4) were identified with activation z scores ≥ |2|, p-value between 1.06e-3 to 1.45e-14 and log2FC > |0.58| at the first time point (Supplementary Table 3).…”

Section: Resultsmentioning

confidence: 99%

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Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics

Emam

Cánovas

Islas‐Trejo

et al. 2020

Sci Rep

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Reactive Nitrogen Species (RNS) are a group of bactericidal molecules produced by macrophages in response to pathogens in a process called oxidative burst. Nitric oxide (NO −) is a member of RNS produced from arginine by inducible Nitric Oxide Synthase (iNOS) enzyme. The activity of iNOS and production of NO − by macrophages following stimulation is one of the indicators of macrophage polarization towards M1/proinflammatory. Production of NO − by bovine monocyte-derived macrophage (MDM) and mouse peritoneal macrophages has been shown to be strongly associated with host genetic with the heritability of 0.776 in bovine MDM and 0.8 in mouse peritoneal macrophages. However, the mechanism of genetic regulation of macrophage response has remained less explored. In the current study, the transcriptome of bovine MDMs was compared between two extreme phenotypes that had been classified as high and low responder based on NO − production. The results showed that 179 and 392 genes were differentially expressed (DE) between high and low responder groups at 3 and 18 hours after exposure to Escherichia coli, respectively. A set of 11 Transcription Factors (TFs) (STAT1,

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Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics

Emam

Cánovas

Islas‐Trejo

et al. 2020

Sci Rep

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“…Preparation of BMDMs. BMDMs were differentiated from bone marrow isolated from the femur and tibia of 8-to 16-wk-old C57BL/6 mice, as described previously (45). Briefly, bone marrow cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Wisent) containing 10% heat-inactivated FBS, antibiotics, and 20% L cell-conditioned medium (LCCM).…”

Section: Methodsmentioning

confidence: 99%

Rocaglates as dual-targeting agents for experimental cerebral malaria

Langlais

Cencic

Moradin

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in parasites. Rocaglates are a class of natural products derived from plants of the genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis. Here, we show that the rocaglate CR-1-31B perturbs association of eIF4A (PfeIF4A) with RNA. CR-1-31B shows potent prophylactic and therapeutic antiplasmodial activity in vivo in mouse models of infection with (CM) and (blood-stage malaria), and can also block replication of different clinical isolates of in human erythrocytes infected ex vivo including drug-resistant isolates. In vivo, a single dosing of CR-1-31B in-infected animals is sufficient to provide protection against lethality. CR-1-31B is shown to dampen expression of the early proinflammatory response in myeloid cells in vitro and dampens the inflammatory response in vivo in -infected mice. The dual activity of CR-1-31B as an antiplasmodial and as an inhibitor of the inflammatory response in myeloid cells should prove extremely valuable for therapeutic intervention in human cases of CM.

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“…Flow cytometric gating for the generation of contour plots is shown in Figure S3B. sexual dimorphism in cardiac tissue macrophage transcriptional profiles, such as male upregulation of Irf8, which is linked to chronic inflammation (Langlais et al, 2016). Conversely, the most upregulated gene in female macrophages and the most sexually dimorphic macrophage gene in both sexes ( Figure 5C) is Tsc22d3 (also known as Gilz), a transcription factor implicated in anti-inflammatory functions and a downstream driver of the potent anti-inflammatory effects of glucocorticoids (Eddleston et al, 2007;Ronchetti et al, 2015;Sevilla et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart

et al. 2018

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Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition and highlighted important functional roles for non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-seq). Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations, such as mural cells and glia. Our analyses also revealed extensive networks of intercellular communication and suggested prevalent sexual dimorphism in gene expression in the heart. This study offers insights into the structure and function of the mammalian cardiac cellulome and provides an important resource that will stimulate studies in cardiac cell biology.

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The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation

Cited by 33 publications

References 20 publications

Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics

Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics

Rocaglates as dual-targeting agents for experimental cerebral malaria

Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart

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