Bibliographic Details
| Title: |
Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses |
| Authors: |
Alba Llibre, Nikaïa Smith, Vincent Rouilly, Munyaradzi Musvosvi, Elisa Nemes, Céline Posseme, Simbarashe Mabwe, Bruno Charbit, Stanley Kimbung Mbandi, Elizabeth Filander, Hadn Africa, Violaine Saint-André, Vincent Bondet, Pierre Bost, Humphrey Mulenga, Nicole Bilek, Matthew L. Albert, Thomas J. Scriba, Darragh Duffy |
| Source: |
Frontiers in Immunology, Vol 13 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
tuberculosis, IL-1ra, IL-1, immunometabolism, systems immunology, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
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 the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. This revealed distinct responses between TB/LTBI at transcriptomic, proteomic and metabolomic levels. At baseline, we identified a novel immune-metabolic association between pregnane steroids, the PPARγ pathway and elevated plasma IL-1ra in TB. We observed dysregulated IL-1 responses after BCG stimulation in TB patients, with elevated IL-1ra responses being explained by upstream TNF differences. Additionally, distinct secretion of IL-1α/IL-1β in LTBI/TB after BCG stimulation was associated with downstream differences in granzyme mediated cleavage. Finally, IL-1β driven signalling was dramatically perturbed in TB disease but was completely restored after successful treatment. This study improves our knowledge of how immune responses are altered during TB disease, and may support the design of improved preventive and therapeutic tools, including host-directed strategies. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2022.897193/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2022.897193 |
| Access URL: |
https://doaj.org/article/6065dbee52904e8581bc7ef2952a2c96 |
| Accession Number: |
edsdoj.6065dbee52904e8581bc7ef2952a2c96 |
| Database: |
Directory of Open Access Journals |
