Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA108315 | ENA |
REPOSITORIES: ENA
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Project description:The inhibitory axis of PD-1 expressed on T cells and its ligands produced by APCs mediates T cell exhaustion in chronic viral infection. We asked whether temporality of the infectious process is decisive for regulation through PD-1/PD-Ligand and investigated its impact on chronic bacterial infection. Here we show that M. tuberculosis and its lipid compounds induce expression of PD-Ligand on dendritic cells (DC). Upregulation of PD-Ligand depended on signaling through DC-SIGN upon infection. As a counterpart, expression of the PD-1 receptor was increased on T cells from tuberculosis patients and PPD+ donors compared to healthy normal individuals. Moreover, PD-1 expressing T cells were confined to granulomatous lesions in tuberculous lungs. Finally, functional blocking of PD-Ligand rescued antigen-specific T cell responses of tuberculosis patients. Taken together, we demonstrate that the inhibitory axis of PD-1/PD-Ligand is operative in mycobacterial infection and suggest inhibition of inhibition for rescuing exhausted T cells in tuberculosis. Keywords: Agilent two-color catolog 44K human whole genome microarrays
2008-02-01 | GSE10198 | GEO
Project description:The inhibitory axis of PD-1 expressed on T cells and its ligands produced by APCs mediates T cell exhaustion in chronic viral infection. We asked whether temporality of the infectious process is decisive for regulation through PD-1/PD-Ligand and investigated its impact on chronic bacterial infection. Here we show that M. tuberculosis and its lipid compounds induce expression of PD-Ligand on dendritic cells (DC). Upregulation of PD-Ligand depended on signaling through DC-SIGN upon infection. As a counterpart, expression of the PD-1 receptor was increased on T cells from tuberculosis patients and PPD+ donors compared to healthy normal individuals. Moreover, PD-1 expressing T cells were confined to granulomatous lesions in tuberculous lungs. Finally, functional blocking of PD-Ligand rescued antigen-specific T cell responses of tuberculosis patients. Taken together, we demonstrate that the inhibitory axis of PD-1/PD-Ligand is operative in mycobacterial infection and suggest inhibition of inhibition for rescuing exhausted T cells in tuberculosis. Experiment Overall Design: Human PBMC-derived DCs were grown in 6-well plates and stimulated for 18 h with either mycobacterial ManLAM or recombinantly expressed ICAM-3. To ensure complete naïve status of DCs before stimulation, cells were left in wells from the day of PBMC isolation until end of stimulation. Change of medium was performed by carefully removing medium from wells without any manipulation of DCs. After stimulation, total RNA was isolated as described above and labeled with Fluorescent Direct Labeling Kit (Agilent Technologies) following manufacturerâs protocols. Microarray experiments were performed as two-color dye-reversal hybridizations. To compensate for dye-specific effects, a color swap was performed. Labeled RNA was hybridized on Whole Human Genome Oligo Microarray Kit 44k Format and scanned using an Agilent scanner according to manufacturerâs protocol (Agilent Technologies). Image analysis was performed using Feature Extractor software (Agilent Technologies). For data analysis Rosetta Resolver software was used (Rosetta Inpharmatics).
2008-06-18 | E-GEOD-10198 | biostudies-arrayexpress
Project description:Multifaceted dysfunction of infant airway macrophages in response to Mycobacterium tuberculosis
2025-01-23 | E-MTAB-7679 | ExpressionAtlas
Project description:Rationale: T cell activation is a key antimicrobial component against mycobacterial disease. Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect the antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the influence of blocking this pathway in pulmonary Mycobacterium avium-intracellulare complex (MAC) infection was not fully understood. Objective: We aimed to determine the influence of genetic depletion of PD-1/PD-L1 pathway on the disease activity of MAC infection. Methods: Wild-type, PD-1-deficient mice and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Measurements and Main Results: The depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in mice infected with MAC. However, remarkable infiltration of CD8 T lymphocytes was observed in the lungs of PD-1 and PD-L1 deficient mice compared to wild-type mice. Comprehensive transcriptome analysis showed that levels of gene expressions related to Th1 immunity did not differ according to the genotypes. However, genes related to the activity of CD8 T cells and related chemokine activity were up-regulated in the infected lungs of PD-1 and PD-L1 deficient mice. Conclusions: Depletion of PD-1/PD-L1 pathway did not affect the activation of Th1 immunity in response to MAC infection, which may explain why MAC infection was controlled in these mice. In addition, CD8-positive T cell pulmonary inflammation in knockout mice might have some clinical implication in the treatment of cancer patients with immune checkpoint inhibitors when the patients are infected with MAC.
2021-09-15 | GSE169202 | GEO
Project description:Tuberculosis patients blood gene expression through treatment
2025-01-24 | E-GEOD-31348 | ExpressionAtlas
Project description:DC-SIGN is a C-type lectin expressed by dendritic cells (DCs) that binds HIV-1, sequestering it within multivesicular bodies to facilitate transmission to CD4+ T cells. Here we characterize the molecular basis of signalling through DC-SIGN by large-scale gene expression profiling and phosphoproteome analysis. Solitary DC-SIGN activation leads to a phenotypically disparate transcriptional program from Toll-like receptor (TLR) triggering with downregulation of MHC II, CD86, and interferon response genes and with induction of the TLR negative regulator ATF3. Phosphoproteome analysis reveals DC-SIGN signals through the leukemia-associated Rho guanine nucleotide exchange factor (LARG) to induce Rho activity. This LARG activation also occurs on DC HIV exposure and is required for effective HIV viral synapse formation. Taken together HIV mediated DC-SIGN signalling provides a mechanism by which HIV evades the immune response yet induces viral spread. Keywords: Activation state, signalling, Toll-like Receptor (TLR)
2007-04-24 | GSE6090 | GEO
Project description:DC-SIGN is a C-type lectin expressed by dendritic cells (DCs) that binds HIV-1, sequestering it within multivesicular bodies to facilitate transmission to CD4+ T cells. Here we characterize the molecular basis of signalling through DC-SIGN by large-scale gene expression profiling and phosphoproteome analysis. Solitary DC-SIGN activation leads to a phenotypically disparate transcriptional program from Toll-like receptor (TLR) triggering with downregulation of MHC II, CD86, and interferon response genes and with induction of the TLR negative regulator ATF3. Phosphoproteome analysis reveals DC-SIGN signals through the leukemia-associated Rho guanine nucleotide exchange factor (LARG) to induce Rho activity. This LARG activation also occurs on DC HIV exposure and is required for effective HIV viral synapse formation. Taken together HIV mediated DC-SIGN signalling provides a mechanism by which HIV evades the immune response yet induces viral spread. Experiment Overall Design: Circulating monocyte derived DCs were isolated from buffy coats by adherence and culture in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). DC preparations analyzed were more than 98% pure. At day four 10 million immature DCs were either left unstimulated or stimulated using plate bound anti-DC-SIGN antibody for 2 hr. Three replicates of non-stimulated or stimulated cells were taken and used to extract total RNA.
2008-06-14 | E-GEOD-6090 | biostudies-arrayexpress
Project description:Transcription profiling by array of human dendritic cells and macrophages infected with Mycobacterium tuberculosis
2025-01-22 | E-MEXP-3521 | ExpressionAtlas
Project description:Hepatitis B virus (HBV) is a leading cause of liver-related diseases and mortality. However, immune mechanisms governing the phases of HBV infection remain elusive. Understanding molecular components in hepatitis immunosuppression and progression is essential for developing immunotherapies for functional cure of chronic HBV infection. Our integrative analysis of intrahepatic tissue and peripheral PBMC samples from patients with acute and chronic HBV infection using single-cell RNA sequencing (scRNA-seq) and TCR/BCR sequencing (scTCR/BCR-seq) revealed three distinct lineages of PBMC-derived intrahepatic T lymphocytes (hpCTLs): exhausted GZMK+PDCD1+, short-lived effector KLRG1+, and inactivated GZMB+PRF1+ hpCTLs. Key factors such as FasL/Fas-mediated cytotoxicity, CD28 co-stimulation, and exhaustion status were identified as determinants of hpCTL functionality. Liver-resident DC-SIGN+ macrophages were found to act as antigen-presenting cells that cross-prime hpCTLs in response to IL-2 or as suppressive macrophages by inhibiting T cell immunity through IL-10 and PD-L1 production and Treg recruitment. The intrahepatic core cellular network, including DC-SIGN+ macrophages, CSF1+ST2+ mast cells, AREG+ liver-resident NK cells, CD14+ hepatocytes, and CXCL13+ TFH, was observed to modulate immune tolerance, activation, and suppression in HBV infection. This study inferred the core cellular network involved in immune phenotype switching across different hepatitis B phases and suggested potential immunomodulatory strategies for treating chronic HBV infection.
2024-12-05 | GSE283471 | GEO
Project description:DC-SIGN+ monocyte-derived dendritic cells (mo-DCs) play important roles in bacterial infections and inflammatory diseases, but the factors regulating their differentiation and proinflammatory status remain poorly defined. Here, we identify a micro-RNA, miR-181a, and a molecular mechanism that simultaneously regulate the acquisition of DC-SIGN+ expression and the activation state of DC-SIGN+ mo-DCs. Specifically, we show that miR-181a promotes DC-SIGN expression during terminal mo-DC differentiation and limits its sensitivity and responsiveness to TLR triggering and CD40 ligation. Mechanistically, miR-181a sustains ERK-MAPK signaling in mo-DCs, thereby enabling the maintenance of high levels of DC-SIGN and a high activation threshold. Low miR-181a levels during mo-DC differentiation, induced by inflammatory signals, do not support the high phospho-ERK signal transduction required for DC-SIGNhi mo-DCs and lead to development of proinflammatory DC-SIGNlo/- mo-DCs. Collectively, our study demonstrates that high DC-SIGN expression levels and a high activation threshold in mo-DCs are linked and simultaneously maintained by miR-181a.
2020-03-10 | GSE96847 | GEO