Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional profiling of the tuberculin skin test in patients with active and latent tuberculosis

ABSTRACT: Transcriptome at the site of a 48 hour tuberculin skin test (TST) and saline injection from patients with active TB disease and latent TB infection

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Gabriele Pollara

PROVIDER: E-MTAB-6816 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease.

Pollara Gabriele G Turner Carolin T CT Rosenheim Joshua J Chandran Aneesh A Bell Lucy C K LCK Khan Ayesha A Patel Amit A Peralta Luis Felipe LF Folino Anna A Akarca Ayse A Venturini Cristina C Baker Tina T Ecker Simone S Ricciardolo Fabio L M FLM Marafioti Teresa T Ugarte-Gil Cesar C Moore David A J DAJ Chain Benjamin M BM Tomlinson Gillian S GS Noursadeghi Mahdad M

Science translational medicine 20210501 592

Host immune responses at the site of <i>Mycobacterium tuberculosis</i> infection can mediate pathogenesis of tuberculosis (TB) and onward transmission of infection. We hypothesized that pathological immune responses would be enriched at the site of host-pathogen interactions modeled by a standardized tuberculin skin test (TST) challenge in patients with active TB compared to those without disease, and interrogated immune responses by genome-wide transcriptional profiling. We show exaggerated int ...[more]

PMID: 33952677

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Project description:Understanding mechanisms of resistance to M. tuberculosis (M.tb) infection in humans could identify novel therapeutic strategies as it has for other infectious diseases. We hypothesized that monocytes from household contacts of pulmonary tuberculosis patients that failed to convert their tuberculin skin tests (TSTNEG) would respond differently to M.tb infection when compared to matched tuberculin skin test positive controls (TSTPOS). We obtained genome-wide transcriptional profiles of M.tb-infected peripheral blood monocytes from 10 TSTNEG and 18 TSTPOS Ugandans. We used Gene Set Enrichment Analysis and interaction networks to identify cellular processes associated with TST status. We discovered gene sets associated with histone deacetylases that were differentially expressed when comparing TSTPOS and TSTNEG subjects. We used small molecule inhibitors to demonstrate that histone deacetylase function is important for the pro-inflammatory response to M.tb infection in monocytes. Monocytes from individuals who appear to resist M.tb infection differentially activate pathways controlled by histone deacetylase in response to M.tb infection when compared to those who are susceptible to infection. These data identify a potential cellular mechanism underlying the clinical phenomenon of persistently negative tuberculin skin tests despite known exposure to an infectious contact. CD14+ monocytes from 18 TSTPOS and 10 TSTNEG subjects were isolated by positive selection. Depending on the yield, between 5E5 and 1E6 monocytes were plated in duplicate in a 24-well tissue culture plate and rested overnight at 37oC, 5% CO2. The next day, cells were mock-infected or infected with virulent M. tuberculosis strain H37Rv at a multiplicity of infection (MOI) 10:1. After a six hour incubation at 37C, 5% CO2, the mycobacteria were killed and total RNA harvested using TRIzol-LS (Invitrogen). TRIzol samples were stored at -80oC until all infections were completed. To minimize batch effects, equal numbers of TSTPOS and TSTNEG subjects were processed on each of six days and frozen aliquots of M.tb were used for infections. RNA was extracted using the RNeasy Mini Kit with on-column DNAse digestion. RNA was transcribed into complementary DNA, labeled, and hybridized onto Illumina HT-12 microarrays according to the manufacturerâs instructions. Probe intensities were quantified using Illumina iScan platform and processed using BeadArray without performing normalization or background correction.

Dataset Information

Transcriptional profiling of the tuberculin skin test in patients with active and latent tuberculosis

Publications

Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease.

Similar Datasets

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