Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lung epithelial signaling mediates early vaccine-induced CD4+ T cell activation and Mtb control

ABSTRACT: Tuberculosis (TB) is the leading cause of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (Mtb) infection is urgently needed. Complete and early Mtb control can be induced in M. bovis Bacillus Calmette–Guérin (BCG) vaccinated hosts when the innate immune response is targeted to generate effective vaccine-induced immunity. In the present study, we show that the superior and early Mtb control that is mediated by innate activation of DCs is associated with mucosal localization of clonal activated vaccine-induced CD4+ T cells in the lung. Our studies also show that the lung epithelial cell signaling through the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB pathway is critical for the mucosal localization of activated vaccine-induced CD4+ T cells for rapid Mtb control. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control.

ORGANISM(S): Mus musculus

PROVIDER: GSE150657 | GEO | 2021/09/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Mucosal exposure to non-tuberculous mycobacteria elicits B-cell mediated protection against pulmonary tuberculosis

Project description:Bacille Calmette Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTM), a distinct lineage from Mtb, are opportunistic pathogens present in the environment. TB endemic countries experience higher exposure to NTM, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy. Therefore, we developed a mouse model (BCG+NTM) that mimics human BCG vaccination at an early stage and continuous NTM exposure via the oral route, including during TB infection. Our results show that BCG+NTM mice had improved protection against pulmonary TB correlating with increased pulmonary influx of B-cells, higher titers of anti-Mtb IgA and IgG antibodies in serum and airways, compared to mice vaccinated with BCG alone. Notably, the lungs of BCG+NTM mice developed B-cell aggregates expressing markers of germinal center formation as determined by spatial transcriptomics. We conclude a direct correlation between NTM exposure and protection from TB, with B-cells playing a crucial role.

2022-10-23 | GSE203037 | GEO

Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (LAM30 IgM)

Project description:Increasing evidence supports a role ofthat antibodies in thecan defense protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially at in the mucosal airways level, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses that were associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) compared to uncontrolled infection (TB) in nonhuman primates. We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to and two- and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays

2024-01-10 | GSE243657 | GEO

Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (NAPPA IgG)

2024-01-10 | GSE243661 | GEO

Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (NAPPA IgA)

2024-01-10 | GSE243660 | GEO

Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (LAM63 IgA)

2024-01-10 | GSE243658 | GEO

Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (LAM63 IgG)

2024-01-10 | GSE243659 | GEO

RNA-Seq analysis of the TB-019 GSK M72/AS01E trial

Project description:This project involves RNA-Seq analysis of samples obtained from the Phase IIA clinical trial TB-019 (NCT01669096) which evaluated kinetics of response, safety, and immunogenicity of the GSK Mycobacterium tuberculosis (MTB) vaccine M72/AS01E (“GSK M72”). GSK M72 consists of the M72 recombinant fusion of Mycobacterium tuberculosis (MTB) proteins Rv0125 and Rv1196 in combination with the liposome, TLR4 ligand (MPL), and QS21 saponin adjuvant AS01E (Leroux-Roels et al., 2013).

2023-12-30 | GSE102574 | GEO

Mycobacterium tuberculosis infection drives a Type I IFN signature in lung lymphocytes

Project description:Mycobacterium tuberculosis (Mtb) infects a quarter of the world’s population and causes tuberculosis (TB), which is a leading cause of death globally. A clear understanding of the dynamics of immune response at cellular level is crucial to design better strategies to control TB. We have employed single-cell RNA-seq approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show enrichment of type I IFN responsive phenotypes among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We have identified Ly6A as a novel lymphoid cell activation marker and validated its upregulation in activated lymphoid cells post Mtb infection. The cross analysis of type I IFN signature in human TB infected peripheral blood samples further validates our results. These findings significantly contribute toward understanding and characterizing the transcriptional parameters at single-cell depth in a highly relevant and reproducible mouse model of TB.

2022-06-24 | GSE200639 | GEO

Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine

Project description:RhCMV-based TB vaccines are able to elicit and maintain immune effector responses that can control Mtb at the earliest stages of infection, and the protection afforded by this vaccine can be complete, if not sterilizing. To our knowledge, this is the first demonstration of complete prevention of TB disease in Rhesus Macaques (RM) by a long-acting vaccine after highly pathogenic (Erdman strain) Mtb challenge.

2017-12-26 | GSE102440 | GEO

Changes in the Membrane-Associated Proteins of Exosomes Released from Human Macrophages after Mycobacterium tuberculosis Infection - Biotinylated

Project description:Tuberculosis (TB) is the deadliest infectious disease worldwide. One obstacle hindering the elimination of TB is our lack of understanding of host-pathogen interactions. Exosomes, naturally loaded with microbial molecules, are circulating markers of TB. Changes in the host protein composition of exosomes from Mycobacterium tuberculosis (Mtb)-infected cells have not been described, can contribute to our understanding of the disease process, and serve as a direct source of biomarkers or as capture targets to enrich for exosomes containing microbial molecules. Here, the protein composition of exosomes from Mtb-infected and uninfected THP-1-derived macrophages was evaluated by tandem-mass-spectrometry and differences in protein abundances were assessed. Our results show that infection with Mtb leads to significant changes in the protein composition of exosomes. Specifically, 41 proteins were significantly more abundant in exosomes from Mtb-infected cells; 63% of these were predicted to be membrane associated. Thus, we used a novel biotinylation strategy to verify protein localization, and confirmed the localization of some of these proteins in the exosomal membrane. Our findings reveal another important scenario where Mtb could be influencing changes in host cells that unveil new features of the host-pathogen interaction and may also be exploited as a source of biomarkers for TB.

2018-08-06 | PXD010659 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data