Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA150635 | ENA |
REPOSITORIES: ENA
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Project description:Tissue resident memory T cells (TRM) provide superior protection against infection localised to extra-lymphoid compartments in the body. Here we show that CD103+CD8+ TRM cells develop in skin from killer cell lectin-like receptor (KLR)G1-negative precursors that selectively infiltrate the epithelial layer. In the skin, a combination of chemokine-guided epithelial entry, local interleukin (IL)-15 and transforming growth factor (TGF)-β signalling is required for formation and survival of these long-lived memory cells. Importantly, TRM differentiation results in the gradual acquisition of a unique transcriptional profile that differs from that expressed by memory cells in the circulation and other types of skin-resident intra-epithelial T cells, such as the dendritic epidermal T cells (DETC). We provide a comprehensive molecular and developmental framework for the local differentiation of a distinct type of peripheral memory T cell that contributes to an important first-line of immune defence in barrier tissues such as skin and mucosa. 24 samples were analyzed: 3 replicates of memory gB-T CD8+. CD103+ T cells isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of memory P14 CD8+ T cells isolated from gut of mice on day 60 p.i. with LCMV Armstrong. 3 replicates of memory gB-T CD8+ T cells from the lung of mice on day 30 p.i. with influenza WSN. 3 replicates of memory CD62L high CD8+ T cells from the spleen of mice on day 30 p.i. with HSV KOS. 3 replicates of memory CD62L low CD8+ T cells from the spleen of mice of day 30 p.i. with HSV KOS. 3 replicates of γδ-DETC isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of αβ-DETC from naive TCRδ-/- mice; and 3 replicates of naive gB-T CD8+ T cells from the spleen of naive gB-T transgenic mice.
2013-10-01 | E-GEOD-47045 | biostudies-arrayexpress
Project description:Transcriptome analysis of monocytes directly exposed to cell-to-cell contact with Natural Killer (NK) cells or separated by a transwell membrane and their subsequent monocyte-derived dendritic cells. The role of Natural Killer (NK) cells in the early differentiation of monocytes into dendritic cells (DCs) is poorly understood. Their interaction is thought to be restricted to a bilateral cross talk of soluble cytokines. However, many authors have shown that NK cells effect over myeloid cells is dependent on direct cell-to-cell contact. In order to understand what determines a major effect of NK cells over monocytes and their derived DCs, total RNA samples from purified monocytes and monocyte-derived DCs, exposed to direct contact with NK cells or separated by a transwell membrane were amplified and hybridized to the Affymetrix Human GeneChip 2.0 ST array. Analyses were performed using BRB-ArrayTools version 4.5.0, developed by Dr. Richard Simon and the BRB-ArrayTools Development Team. We found that compared to untouched monocytes, cell-to-cell contact with NK cells modified the expression of 283 genes whereas contact through a transwell membrane modified the expression of 35 genes. After differentiation and compared to DCs derived from untouched monocytes, DCs derived from monocytes allowed to direct cell-to-cell contact with NK cells had the expression of 128 genes modified whereas DCs derived from monocytes primed through a transwell membrane had only 2 genes modified. Our results suggested that cell-to-cell interactions with NK cells are important to imprint a stable transcriptional program in monocytes lasting even after their further differentiation into DCs.
2018-07-03 | GSE116487 | GEO
Project description:Herpes simplex virus type 1 (HSV-1) is the prototype of the α-herpesvirus family. To propagate within the host organism, HSV-1 has evolved several strategies to subvert the host immune response. Due to the pivotal role of dendritic cells (DCs), bridging innate and adaptive immunity and activating naïve T cells, they represent an attractive target for HSV-1-triggered immune regulation. Here, we report a novel HSV-1-mediated mechanism of signal transducer and activator of transcription 3 (STAT3) dysregulation in human monocyte-derived mature DCs (mDCs). Due to STAT3’s antiviral activity, STAT3 was shown to be modulated by viruses to efficiently replicate in several different cell types, however, not in DCs. We show that HSV-1 infection of mDCs leads to diminished total STAT3 expression and STAT3 phosphorylation (pSTAT3), as well as downregulation of STAT3 mRNA very early upon infection. Protein downregulation of STAT3 could be verified by label-free mass spectrometric analysis of HSV-1- and HSV-2-infected mDCs. We found that two viral proteins, the tegument protein virion host shutoff (vhs) and the immediate early (IE) protein ICP27, contribute to STAT3 protein downregulation upon HSV-1 infection. However, HSV-1 Δvhs and ΔICP27 deletion strains still inhibited pSTAT3 in infected mDCs, suggesting that different viral proteins impair STAT3 phosphorylation and total STAT3. Moreover, STAT3 protein levels were degraded in a proteasome-dependent, but apoptosis-independent manner. Taken together, we demonstrate that HSV-1 downregulates STAT3 in HSV-1-infected human mDCs at the transcript, protein and phosphorylation levels. Downregulation of STAT3 protein depended on vhs and the proteasome, very likely to shape DC function for immune evasion and modulation.
2026-07-22 | PXD081438 | Pride
Project description:Herpes simplex virus type 1 (HSV-1) is the prototype of the α-herpesvirus family. To propagate within the host organism, HSV-1 has evolved several strategies to subvert the host immune response. Due to the pivotal role of dendritic cells (DCs), bridging innate and adaptive immunity and activating naïve T cells, they represent an attractive target for HSV-1-triggered immune regulation. Here, we report a novel HSV-1-mediated mechanism of signal transducer and activator of transcription 3 (STAT3) dysregulation in human monocyte-derived mature DCs (mDCs). Due to STAT3’s antiviral activity, STAT3 was shown to be modulated by viruses to efficiently replicate in several different cell types, however, not in DCs. We show that HSV-1 infection of mDCs leads to diminished total STAT3 expression and STAT3 phosphorylation (pSTAT3), as well as downregulation of STAT3 mRNA very early upon infection. Protein downregulation of STAT3 could be verified by label-free mass spectrometric analysis of HSV-1- and HSV-2-infected mDCs. We found that two viral proteins, the tegument protein virion host shutoff (vhs) and the immediate early (IE) protein ICP27, contribute to STAT3 protein downregulation upon HSV-1 infection. However, HSV-1 Δvhs and ΔICP27 deletion strains still inhibited pSTAT3 in infected mDCs, suggesting that different viral proteins impair STAT3 phosphorylation and total STAT3. Moreover, STAT3 protein levels were degraded in a proteasome-dependent, but apoptosis-independent manner. Taken together, we demonstrate that HSV-1 downregulates STAT3 in HSV-1-infected human mDCs at the transcript, protein and phosphorylation levels. Downregulation of STAT3 protein depended on vhs and the proteasome, very likely to shape DC function for immune evasion and modulation.
2026-07-23 | PXD081503 | Pride
Project description:Herpes simplex virus type 1 (HSV-1) is the prototype of the α-herpesvirus family. To propagate within the host organism, HSV-1 has evolved several strategies to subvert the host immune response. Due to the pivotal role of dendritic cells (DCs), bridging innate and adaptive immunity and activating naïve T cells, they represent an attractive target for HSV-1-triggered immune regulation. Here, we report a novel HSV-1-mediated mechanism of signal transducer and activator of transcription 3 (STAT3) dysregulation in human monocyte-derived mature DCs (mDCs). Due to STAT3’s antiviral activity, STAT3 was shown to be modulated by viruses to efficiently replicate in several different cell types, however, not in DCs. We show that HSV-1 infection of mDCs leads to diminished total STAT3 expression and STAT3 phosphorylation (pSTAT3), as well as downregulation of STAT3 mRNA very early upon infection. Protein downregulation of STAT3 could be verified by label-free mass spectrometric analysis of HSV-1- and HSV-2-infected mDCs. We found that two viral proteins, the tegument protein virion host shutoff (vhs) and the immediate early (IE) protein ICP27, contribute to STAT3 protein downregulation upon HSV-1 infection. However, HSV-1 Δvhs and ΔICP27 deletion strains still inhibited pSTAT3 in infected mDCs, suggesting that different viral proteins impair STAT3 phosphorylation and total STAT3. Moreover, STAT3 protein levels were degraded in a proteasome-dependent, but apoptosis-independent manner. Taken together, we demonstrate that HSV-1 downregulates STAT3 in HSV-1-infected human mDCs at the transcript, protein and phosphorylation levels. Downregulation of STAT3 protein depended on vhs and the proteasome, very likely to shape DC function for immune evasion and modulation.
2026-07-21 | PXD081194 | Pride
Project description:Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of IRF-3, NF-κB and type I interferon (IFN) signaling. Here, we used highly multiplexed proteomics to quantify >8,000 cellular proteins and ~80% of viral proteins over seven time points spanning the whole course of VACV infection. This identified multiple novel viral targets, including putative natural killer cell ligands and IFN-stimulated genes. The class II histone deacetylase HDAC5 was selectively degraded early during VACV infection. Use of cell lines in which HDAC5 was overexpressed or knocked out showed that HDAC5 restricted replication of both VACV and herpes simplex virus type 1 (HSV-1). By generating a protein-based temporal classification of VACV gene expression, we identified the early protein C6, a multifunctional IFN antagonist, as the factor that targets HDAC5 for proteasomal degradation. Our approach thus identifies both a novel restriction factor and a viral mechanism of innate immune evasion.
2019-05-07 | PXD012785 | Pride
Project description:Herpes simplex virus type 1 (HSV-1) infects dendritic cells (DCs), professional antigen-presenting cells that initiate and regulate host antiviral responses. HSV-1 infects DCs limiting their maturation, migration to draining lymph nodes and T cell activation capacity, ultimately promotes their apoptosis. Here, we investigated the impact of HSV-1 infection over neutral lipid metabolism in DCs and their function. We found that HSV-1 significantly alters neutral lipid metabolism in infected DCs and promotes LD accumulation. Pharmacological inhibition of cholesterol ester synthesis, or fatty acid transporter proteins in infected DCs reduced LD accumulation and viral replication, enhanced DC viability and DC migration to draining lymph nodes and promoted DC priming of virus-specific CD8+ T cells. These findings highlight the role of neutral lipid metabolism in HSV-1-infected DCs and its impact over host immunity against this virus, underscoring lipid metabolism in DCs as a potential therapeutical target for triggering antiviral immunity against HSV-1.
2025-04-03 | MTBLS5163 | MetaboLights
Project description:It is increasingly recognized that immune development within mucosal tissues is under the control of environmental factors during early life. However, the cellular mechanisms that underlie such temporally and regionally restrictive governance of these processes is unclear. Here, we uncover an extrathymic pathway of immune development within the colon that is controlled by embryonic, but not bone-marrow derived, macrophages which determines the ability of these organs to receive invariant natural killer T (iNKT) cells and allow them to establish local residency. Consequently, early life perturbations of fetal-derived macrophages result in persistent decreases of mucosal iNKT cells and is associated with later life susceptibility or resistance to iNKT cell associated mucosal disorders. These studies uncover a host developmental program orchestrated by ontogenically distinct macrophages that is regulated by microbiota and reveal an important post-natal function of macrophages that emerge in fetal life.
2021-03-31 | GSE167973 | GEO
Project description:It is increasingly recognized that immune development within mucosal tissues is under the control of environmental factors during early life. However, the cellular mechanisms that underlie such temporally and regionally restrictive governance of these processes is unclear. Here, we uncover an extrathymic pathway of immune development within the colon that is controlled by embryonic, but not bone-marrow derived, macrophages which determines the ability of these organs to receive invariant natural killer T (iNKT) cells and allow them to establish local residency. Consequently, early life perturbations of fetal-derived macrophages result in persistent decreases of mucosal iNKT cells and is associated with later life susceptibility or resistance to iNKT cell associated mucosal disorders. These studies uncover a host developmental program orchestrated by ontogenically distinct macrophages that is regulated by microbiota and reveal an important post-natal function of macrophages that emerge in fetal life.
2021-03-31 | GSE167970 | GEO
Project description:It is increasingly recognized that immune development within mucosal tissues is under the control of environmental factors during early life. However, the cellular mechanisms that underlie such temporally and regionally restrictive governance of these processes is unclear. Here, we uncover an extrathymic pathway of immune development within the colon that is controlled by embryonic, but not bone-marrow derived, macrophages which determines the ability of these organs to receive invariant natural killer T (iNKT) cells and allow them to establish local residency. Consequently, early life perturbations of fetal-derived macrophages result in persistent decreases of mucosal iNKT cells and is associated with later life susceptibility or resistance to iNKT cell associated mucosal disorders. These studies uncover a host developmental program orchestrated by ontogenically distinct macrophages that is regulated by microbiota and reveal an important post-natal function of macrophages that emerge in fetal life.
2021-03-31 | GSE167951 | GEO