Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles
Abstract In vitro whole blood infection models are used for elucidating the immune response to Mycobacterium tuberculosis (Mtb). They exhibit commonalities but also differences, to the in vivo blood transcriptional response during natural human Mtb disease. Here, we present a description of concorda...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-10-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-20409-y |
| _version_ | 1828096290824650752 |
|---|---|
| author | Petra Bachanová Ashleigh Cheyne Claire Broderick Sandra M. Newton Michael Levin Myrsini Kaforou |
| author_facet | Petra Bachanová Ashleigh Cheyne Claire Broderick Sandra M. Newton Michael Levin Myrsini Kaforou |
| author_sort | Petra Bachanová |
| collection | DOAJ |
| description | Abstract In vitro whole blood infection models are used for elucidating the immune response to Mycobacterium tuberculosis (Mtb). They exhibit commonalities but also differences, to the in vivo blood transcriptional response during natural human Mtb disease. Here, we present a description of concordant and discordant components of the immune response in blood, quantified through transcriptional profiling in an in vitro whole blood infection model compared to whole blood from patients with tuberculosis disease. We identified concordantly and discordantly expressed gene modules and performed in silico cell deconvolution. A high degree of concordance of gene expression between both adult and paediatric in vivo–in vitro tuberculosis infection was identified. Concordance in paediatric in vivo vs in vitro comparison is largely characterised by immune suppression, while in adults the comparison is marked by concordant immune activation, particularly that of inflammation, chemokine, and interferon signalling. Discordance between in vitro and in vivo increases over time and is driven by T-cell regulation and monocyte-related gene expression, likely due to apoptotic depletion of monocytes and increasing relative fraction of longer-lived cell types, such as T and B cells. Our approach facilitates a more informed use of the whole blood in vitro model, while also accounting for its limitations. |
| first_indexed | 2024-04-11T07:26:59Z |
| format | Article |
| id | doaj.art-e3c2a22ddaf24dfd92eb79b321911478 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T07:26:59Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e3c2a22ddaf24dfd92eb79b3219114782022-12-22T04:37:02ZengNature PortfolioScientific Reports2045-23222022-10-0112111310.1038/s41598-022-20409-yComparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profilesPetra Bachanová0Ashleigh Cheyne1Claire Broderick2Sandra M. Newton3Michael Levin4Myrsini Kaforou5Department of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonAbstract In vitro whole blood infection models are used for elucidating the immune response to Mycobacterium tuberculosis (Mtb). They exhibit commonalities but also differences, to the in vivo blood transcriptional response during natural human Mtb disease. Here, we present a description of concordant and discordant components of the immune response in blood, quantified through transcriptional profiling in an in vitro whole blood infection model compared to whole blood from patients with tuberculosis disease. We identified concordantly and discordantly expressed gene modules and performed in silico cell deconvolution. A high degree of concordance of gene expression between both adult and paediatric in vivo–in vitro tuberculosis infection was identified. Concordance in paediatric in vivo vs in vitro comparison is largely characterised by immune suppression, while in adults the comparison is marked by concordant immune activation, particularly that of inflammation, chemokine, and interferon signalling. Discordance between in vitro and in vivo increases over time and is driven by T-cell regulation and monocyte-related gene expression, likely due to apoptotic depletion of monocytes and increasing relative fraction of longer-lived cell types, such as T and B cells. Our approach facilitates a more informed use of the whole blood in vitro model, while also accounting for its limitations.https://doi.org/10.1038/s41598-022-20409-y |
| spellingShingle | Petra Bachanová Ashleigh Cheyne Claire Broderick Sandra M. Newton Michael Levin Myrsini Kaforou Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles Scientific Reports |
| title | Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles |
| title_full | Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles |
| title_fullStr | Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles |
| title_full_unstemmed | Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles |
| title_short | Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles |
| title_sort | comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients blood rna profiles |
| url | https://doi.org/10.1038/s41598-022-20409-y |
| work_keys_str_mv | AT petrabachanova comparativetranscriptomicanalysisofwholebloodmycobacterialgrowthassaysandtuberculosispatientsbloodrnaprofiles AT ashleighcheyne comparativetranscriptomicanalysisofwholebloodmycobacterialgrowthassaysandtuberculosispatientsbloodrnaprofiles AT clairebroderick comparativetranscriptomicanalysisofwholebloodmycobacterialgrowthassaysandtuberculosispatientsbloodrnaprofiles AT sandramnewton comparativetranscriptomicanalysisofwholebloodmycobacterialgrowthassaysandtuberculosispatientsbloodrnaprofiles AT michaellevin comparativetranscriptomicanalysisofwholebloodmycobacterialgrowthassaysandtuberculosispatientsbloodrnaprofiles AT myrsinikaforou comparativetranscriptomicanalysisofwholebloodmycobacterialgrowthassaysandtuberculosispatientsbloodrnaprofiles |