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

Autor:	Llibre A; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Smith N; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Rouilly V; DATACTIX, Paris, France., Musvosvi M; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Nemes E; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Posseme C; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Mabwe S; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Charbit B; Cytometry and Biomarkers UTechS, CRT, Institut Pasteur, Université Paris Cité, Paris, France., Mbandi SK; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Filander E; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Africa H; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Saint-André V; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France.; Bioinformatics and Biostatistics HUB, Computational Biology Department, Institut Pasteur, Université Paris Cité, Paris, France., Bondet V; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Bost P; Sorbonne Université, Complexité du vivant, Paris, France.; Systems Biology Group, Computational Biology Department, Institut Pasteur, Université Paris Cité, Paris, France., Mulenga H; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Bilek N; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Albert ML; HIBIO, San Francisco, CA, United States., Scriba TJ; South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Duffy D; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France.; Cytometry and Biomarkers UTechS, CRT, Institut Pasteur, Université Paris Cité, Paris, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Dec 14; Vol. 13, pp. 897193. Date of Electronic Publication: 2022 Dec 14 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.897193
Abstrakt:	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. Competing Interests: MLA is a current employee of HIBIO. VR was employed by DATACTIX. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Llibre, Smith, Rouilly, Musvosvi, Nemes, Posseme, Mabwe, Charbit, Mbandi, Filander, Africa, Saint-André, Bondet, Bost, Mulenga, Bilek, Albert, Scriba and Duffy.)
Databáze:	MEDLINE
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