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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [Human_CSF_T_cell_scRNASeq]

ABSTRACT: Define genes expressed by CD4 and CD8 T cells FACS sorted from a CSF specimen of a human subject with HIV-associated tuberculous meningitis

ORGANISM(S): Homo sapiens

PROVIDER: GSE235263 | GEO | 2023/11/06

REPOSITORIES: GEO

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Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy.

Project description:After Mycobacterium tuberculosis (Mtb) infection, many effector T cells traffic to the lungs, but few become activated. Here we use an antigen receptor reporter mouse (Nur77-GFP) to identify recently activated CD4 T cells in the lungs. These Nur77-GFPHI cells contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFPLO cells. By contrast, Nur77-GFPLO cells express markers of terminal exhaustion and cytotoxicity, and the trafficking receptor S1pr5, associated with vascular localization. A short course of immunotherapy targeting OX40+ cells transiently expands CD4 T cell numbers and shifts their phenotype towards parenchymal protective cells. Moreover, OX40 agonist immunotherapy decreases the lung bacterial burden and extends host survival, offering an additive benefit to antibiotics. CD4 T cells from the cerebrospinal fluid of humans with HIV-associated tuberculous meningitis commonly express surface OX40 protein, while CD8 T cells do not. Our data thus propose OX40 as a marker of recently activated CD4 T cells at the infection site and a potential target for immunotherapy in tuberculosis.

| S-EPMC10728168 | biostudies-literature

Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-06 | GSE235800 | GEO

Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [GFP_HI_LO_scRNASeq]

Project description:Define genes differentially expressed by Nur77-GFP HI and LO CD4 T cells FACS sorted from the lungs of Mycobacterium tuberculosis-infected mice

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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [GFP_HI_LO_BULKRNASeq]

Project description:Define genes differentially expressed by Nur77-GFP HI and LO CD4 T cells FACS sorted from the lungs of Mycobacterium tuberculosis-infected mice with bulk RNA seq

2023-11-06 | GSE235564 | GEO

Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [Tetramer_scRNASeq]

Project description:Define genes expressed by CD4 T cells in the lungs of Mycobacterium tuberculosis-infected mice

2023-11-06 | GSE235563 | GEO

Tuberculous Meningitis in Pediatric Patients [CSF]

Project description:Tuberculous Meningitis in Pediatric Patients [CSF]

| PRJNA504827 | ENA

Gene Expression Profiling of Tuberculous Meningitis

Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups. Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.!Series_type = Expression profiling by array

2011-06-30 | E-GEOD-23074 | biostudies-arrayexpress

Value of lipocalin 2 as a potential biomarker for bacterial meningitis

Project description:Objectives: Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome. Methods: We applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam. Results: In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis (BM) other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis), with the sensitivity: 0.88 (95% confident interval (CI): 0.77-0.94), the specificity: 0.91 (95%CI: 0.88-0.94) and the diagnostic odd ratio: 73.8 (95%CI: 31.8-171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under receiver-operating-characteristic-curve 0.96; 95%CI: 0.93-0.99). Conclusions: Our results suggest that LCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections..

2020-08-20 | PXD020510 | Pride

Gene Expression Profiling of Tuberculous Meningitis

2011-07-01 | GSE23074 | GEO

Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy

Project description:Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy

| PRJNA987642 | ENA