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

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 indivi...

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Autores principales: Llibre, Alba, Smith, Nikaïa, Rouilly, Vincent, Musvosvi, Munyaradzi, Nemes, Elisa, Posseme, Céline, Mabwe, Simbarashe, Charbit, Bruno, Mbandi, Stanley Kimbung, Filander, Elizabeth, Africa, Hadn, Saint-André, Violaine, Bondet, Vincent, Bost, Pierre, Mulenga, Humphrey, Bilek, Nicole, Albert, Matthew L., Scriba, Thomas J., Duffy, Darragh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795069/
https://www.ncbi.nlm.nih.gov/pubmed/36591308
http://dx.doi.org/10.3389/fimmu.2022.897193
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author Llibre, Alba
Smith, Nikaïa
Rouilly, Vincent
Musvosvi, Munyaradzi
Nemes, Elisa
Posseme, Céline
Mabwe, Simbarashe
Charbit, Bruno
Mbandi, Stanley Kimbung
Filander, Elizabeth
Africa, Hadn
Saint-André, Violaine
Bondet, Vincent
Bost, Pierre
Mulenga, Humphrey
Bilek, Nicole
Albert, Matthew L.
Scriba, Thomas J.
Duffy, Darragh
author_facet Llibre, Alba
Smith, Nikaïa
Rouilly, Vincent
Musvosvi, Munyaradzi
Nemes, Elisa
Posseme, Céline
Mabwe, Simbarashe
Charbit, Bruno
Mbandi, Stanley Kimbung
Filander, Elizabeth
Africa, Hadn
Saint-André, Violaine
Bondet, Vincent
Bost, Pierre
Mulenga, Humphrey
Bilek, Nicole
Albert, Matthew L.
Scriba, Thomas J.
Duffy, Darragh
author_sort Llibre, Alba
collection PubMed
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 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.
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spelling pubmed-97950692022-12-29 Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses Llibre, Alba Smith, Nikaïa Rouilly, Vincent Musvosvi, Munyaradzi Nemes, Elisa Posseme, Céline Mabwe, Simbarashe Charbit, Bruno Mbandi, Stanley Kimbung Filander, Elizabeth Africa, Hadn Saint-André, Violaine Bondet, Vincent Bost, Pierre Mulenga, Humphrey Bilek, Nicole Albert, Matthew L. Scriba, Thomas J. Duffy, Darragh Front Immunol Immunology 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. Frontiers Media S.A. 2022-12-14 /pmc/articles/PMC9795069/ /pubmed/36591308 http://dx.doi.org/10.3389/fimmu.2022.897193 Text en Copyright © 2022 Llibre, Smith, Rouilly, Musvosvi, Nemes, Posseme, Mabwe, Charbit, Mbandi, Filander, Africa, Saint-André, Bondet, Bost, Mulenga, Bilek, Albert, Scriba and Duffy https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Llibre, Alba
Smith, Nikaïa
Rouilly, Vincent
Musvosvi, Munyaradzi
Nemes, Elisa
Posseme, Céline
Mabwe, Simbarashe
Charbit, Bruno
Mbandi, Stanley Kimbung
Filander, Elizabeth
Africa, Hadn
Saint-André, Violaine
Bondet, Vincent
Bost, Pierre
Mulenga, Humphrey
Bilek, Nicole
Albert, Matthew L.
Scriba, Thomas J.
Duffy, Darragh
Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses
title Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses
title_full Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses
title_fullStr Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses
title_full_unstemmed Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses
title_short Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses
title_sort tuberculosis alters immune-metabolic pathways resulting in perturbed il-1 responses
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795069/
https://www.ncbi.nlm.nih.gov/pubmed/36591308
http://dx.doi.org/10.3389/fimmu.2022.897193
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