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Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses [Luminex]

ABSTRACT: Tuberculosis (TB) remains a major public health problem and we lack a comprehensive understanding of how Mycobacterium tuberculosis (M. tb) infection impacts host immune responses. We compared, at two timepoints, the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. The immune response was stimulated using the TruCulture system with the corresponding stimulations: TB antigen, BCG, 1L1b, and the Luminex xMAP array was used to assess the cytokines expression profile of the samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Vincent Rouilly

PROVIDER: E-MTAB-12380 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses

Project description:Tuberculosis (TB) remains a major public health problem and we lack a comprehensive understanding of how Mycobacterium tuberculosis (M. tb) infection impacts host immune responses. We compared, at two timepoints, the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. The immune response was stimulated using the TruCulture system with the corresponding stimulations: TB antigen, BCG, 1L1b, and the Nanostring platform was used to assess the gene expression profiles of the samples. The Nanostring platform was used to evaluate the gene expression

2022-11-05 | E-MTAB-12379 | biostudies-arrayexpress

Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses [metabolomics]

Project description:Tuberculosis (TB) remains a major public health problem and we lack a comprehensive understanding of how Mycobacterium tuberculosis (M. tb) infection impacts host immune responses. We compared, at two timepoints, the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. The immune response was assessed using the TruCulture system with a Null stimulation. samples were tested by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC MS/MS) for a total of 696 metabolites.

2022-11-05 | E-MTAB-12381 | biostudies-arrayexpress

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

Exploring the potential role of moonlighting function of the surface-associated proteins from Mycobacterium bovis BCG Moreau and Pasteur by comparative proteomic

Project description:Tuberculosis (TB) is one of major causes of death worldwide. Bacillus Calmette-Guerin (BCG) is the only licensed TB vaccine and its inability to protect against adult pulmonary TB can be due to genetic differences among strains described since the 1940s. In this work, we compared the proteomic profile of the surface-associated proteins from M. bovis BCG Moreau, the Brazilian vaccine strain, and the BCG Pasteur reference strain. The methodology used was 2D-gel electrophoresis combined with mass spectrometry techniques (MALDI-TOF/TOF). We identified 115 proteins. Of these, 24 proteins showed differential expression between the two BCG strains. Furthermore, 27 proteins previously described as displaying moonlighting function were identified, 8 of these proteins showed variation in abundance comparing BCG Moreau to Pasteur and 2 of them presented two different domain hits.

2019-05-15 | PXD006141 | Pride

PBMC expression profiles of BCG vaccine protected infants and of BCG vaccinated infants who develop tuberculosis disease

Project description:Analysis of PBMC from 10 week old infants vaccinated with BCG at birth. During follow-up 26 infants developed tuberculosis (TB) (non-protected by BCG) and 20 infants did not develop TB despite documented exposure (protected by BCG). PBMC were stimulated with media only or reconstituted BCG for 4 and 12 hours. Results provide insight into the mechanisms behind the failure of BCG to protect against disease.

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Food-associated Lactiplantibacillus plantarum C9O4 reverts inflammation and apoptosis in intestinal epithelial cells: a proteomic insight

Project description:Nowadays, Western diets and lifestyle lead to an increasing occurrence of chronic gut inflammation, that represents an emerging health concern with still a lack of successful therapies. Fermented foods, and their associated Lactic Acid Bacteria, have recently regained popularity for their probiotic potential including the maintenance of gut homeostasis by modulating the immune and inflammatory response. Our study aims to investigate the cross-talk between the food-borne strain Lactiplantibacillus plantarum C9O4 and intestinal epithelial cells in an in vitro inflammation model. Cytokines profile shows the ability of C9O4 to significantly reduce levels of IL-2, IL-5, IL-6, and IFN-γ. Proteomic functional analysis reveals an active host-microbe interaction that highlights an immunoregulatory role of C9O4, able to revert both the detrimental effects of IFN-γ through the JAK/STAT pathway and the apoptosis process in inflamed cells. These results suggest a promising therapeutic role of fermented food-associated microbes for the management of gastrointestinal inflammatory diseases.

2024-01-26 | PXD042175 | Pride

Transcriptional signature of BCG vaccination

Project description:The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Here, we investigated the BCG-specific gene expression changes induced in PBMCs and CD4 memory T cells by BCG in individuals pre- and 8m post vaccination. We also determined whether reactivity against a peptide pool defined in individuals with controlled latent TB infection (MTB300), and with peptides homologous to peptides found in BCG, was boosted following BCG vaccination.

2021-12-06 | GSE156422 | GEO

Defining Gene Signatures for Protective Immunity to Tuberculosis in the Chinese Cynomolgus Macaque Model

Project description:Gene expression profiles in PPD-stimulated and unstimulated peripherhal blood mononuclear cells isolated from chinese cynomolgus macaques before and after BCG vaccination and before and after M. tuberculosis challenge were compared in animals able to control TB infection and those that developed TB disease in order to identify potential correlates of protection and/or biomarkers of disease. 6 macaques received BCG vaccination prior to challenge and were able to control TB infection (vaccinated controllers). 3 unvaccinated macaques were also able to control TB infection after challenge (unvaccinated controllers) and 3 other unvaccinated macaques developed TB disease and reached humane endpoint criteria (unvaccinated progressors). PBMCs isolated at 8 and 18 weeks post BCG-vaccination from the vaccinated controllers and at 6 weeks post M.tb challenge and at 2 time-points when the animals were naive in all animals were stimulated with PPD. RNA was extracted from the cells and hybridised to and Agilent rhesus macaque GE microarray in a one-colour hybridisation. Gene expression post-vaccination and/or post-challenge was compared with expression before vaccination/challenge when the animals were naive.

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Combinatorial flexibility of cytokine during Human T helper cells differentiation

Project description:Transcriptional analysis of human T cells differentiated in 4 T Helper context ( Th0, Th1, Th2 and Th17) in the presence or not of Interferon alpha We analyzed the transcriptomic profiles of 4 human naives T cells diferentiated in Th0, Th1, Th2 and Th17 in the presence or not of Interferon Alpha. Microarray analyses were performed in 2 time points : 1/ after Day 5 of polarization (= Day5); 2/ after Day 5+ four hours of re-stimulation (=Day 5+ 4H restim) in 3 different donors.

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Transcriptional portrait of M. bovis BCGΔBCG1419c during in vitro planktonic culture

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