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Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis
This article is published by Plos and is also available at https://doi.org/10.1371/journal.ppat.1006425
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| Format: | Article |
| Language: | English |
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PLOS
2023
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| _version_ | 1867613139115180032 |
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| access_status_str | Open Access |
| author | Lundtoft Christian Nausch Norman Owusu-Dabo Ellis Jacobsen Marc Lang Franziska....et al |
| author_browse | Jacobsen Marc Lang Franziska....et al Lundtoft Christian Nausch Norman Owusu-Dabo Ellis |
| author_facet | Lundtoft Christian Nausch Norman Owusu-Dabo Ellis Jacobsen Marc Lang Franziska....et al |
| author_sort | Lundtoft Christian |
| collection | Thesis |
| description | This article is published by Plos and is also available at https://doi.org/10.1371/journal.ppat.1006425 |
| format | Article |
| id | oai:ir.knust.edu.gh:123456789/14598 |
| institution | KNUST (Ghana) |
| language | English |
| last_indexed | 2026-06-10T12:31:23.640Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from KNUSTSpace — Kwame Nkrumah University of Science & Technology (Ghana) |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | PLOS |
| publisherStr | PLOS |
| record_format | dspace |
| source_str | KNUSTSpace — Kwame Nkrumah University of Science & Technology (Ghana) |
| spelling | oai:ir.knust.edu.gh:123456789/14598 Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis Lundtoft Christian Nausch Norman Owusu-Dabo Ellis Jacobsen Marc Lang Franziska....et al This article is published by Plos and is also available at https://doi.org/10.1371/journal.ppat.1006425 T-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 (IL-7) availability and receptivity. Regulation of IL-7 receptor (IL-7R) expression and signalling are key for IL-7-modulated T-cell functions. Aberrant expression of soluble (s) and membrane-associated (m) IL-7R molecules is associated with development of autoim munity and immune failure in acquired immune deficiency syndrome (AIDS) patients. Here we investigated the role of IL-7/IL-7R on T-cell immunity in human tuberculosis. We per formed two independent case-control studies comparing tuberculosis patients and healthy contacts. This was combined with follow-up examinations for a subgroup of tuberculosis patients under therapy and recovery. Blood plasma and T cells were characterised for IL-7/ sIL-7R and mIL-7R expression, respectively. IL-7-dependent T-cell functions were deter mined by analysing STAT5 phosphorylation, antigen-specific cytokine release and by ana lysing markers of T-cell exhaustion and inflammation. Tuberculosis patients had lower soluble IL-7R (p < 0.001) and higher IL-7 (p < 0.001) plasma concentrations as compared to healthy contacts. Both markers were largely independent and aberrant expression normal ised during therapy and recovery. Furthermore, tuberculosis patients had lower levels ofmIL-7R in T cells caused by post-transcriptional mechanisms. Functional in vitro tests indi cated diminished IL-7-induced STAT5 phosphorylation and impaired IL-7-promoted cyto kine release of Mycobacterium tuberculosis-specific CD4+ T cells from tuberculosis patients. Finally, we determined T-cell exhaustion markers PD-1 and SOCS3 and detected increased SOCS3 expression during therapy. Only moderate correlation of PD-1 and SOCS3 with IL-7 expression was observed. We conclude that diminished soluble IL-7R and increased IL-7 plasma concentrations, as well as decreased membrane-associated IL-7R expression in T cells, reflect impaired T-cell sensitivity to IL-7 in tuberculosis patients. These findings show similarities to pathognomonic features of impaired T-cell functions and immune failure described in AIDS patients. KNUST 2023-12-04T15:24:15Z 2023-12-04T15:24:15Z 2017 Article Lundtoft C, Afum-Adjei Awuah A, Rimpler J,Harling K, Nausch N, Kohns M, et al. (2017) Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis 10.1371/journal.ppat.1006425 https://ir.knust.edu.gh/handle/123456789/14598 en application/pdf PLOS |
| spellingShingle | Lundtoft Christian Nausch Norman Owusu-Dabo Ellis Jacobsen Marc Lang Franziska....et al Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis |
| title | Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis |
| title_full | Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis |
| title_fullStr | Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis |
| title_full_unstemmed | Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis |
| title_short | Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis |
| title_sort | aberrant plasma il 7 and soluble il 7 receptor levels indicate impaired t cell response to il 7 in human tuberculosis |
| url | https://ir.knust.edu.gh/handle/123456789/14598 |
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