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The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection

Endoplasmic reticulum (ER) stress plays a major role in several inflammatory disorders. ER stress induces the unfolded protein response (UPR), a conserved response broadly associated with innate immunity and cell metabolic function in various scenarios. Brucella abortus, an intracellular pathogen, t...

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Autores principales: Guimarães, Erika S., Gomes, Marco Túlio R., Sanches, Rodrigo C. O., Matteucci, Kely Catarine, Marinho, Fábio V., Oliveira, Sergio C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842658/
https://www.ncbi.nlm.nih.gov/pubmed/36660548
http://dx.doi.org/10.3389/fimmu.2022.1063221
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author Guimarães, Erika S.
Gomes, Marco Túlio R.
Sanches, Rodrigo C. O.
Matteucci, Kely Catarine
Marinho, Fábio V.
Oliveira, Sergio C.
author_facet Guimarães, Erika S.
Gomes, Marco Túlio R.
Sanches, Rodrigo C. O.
Matteucci, Kely Catarine
Marinho, Fábio V.
Oliveira, Sergio C.
author_sort Guimarães, Erika S.
collection PubMed
description Endoplasmic reticulum (ER) stress plays a major role in several inflammatory disorders. ER stress induces the unfolded protein response (UPR), a conserved response broadly associated with innate immunity and cell metabolic function in various scenarios. Brucella abortus, an intracellular pathogen, triggers the UPR via Stimulator of interferon genes (STING), an important regulator of macrophage metabolism during B. abortus infection. However, whether ER stress pathways underlie macrophage metabolic function during B. abortus infection remains to be elucidated. Here, we showed that the UPR sensor inositol-requiring enzyme 1α (IRE1α) is as an important component regulating macrophage immunometabolic function. In B. abortus infection, IRE1α supports the macrophage inflammatory profile, favoring M1-like macrophages. IRE1α drives the macrophage metabolic reprogramming in infected macrophages, contributing to the reduced oxidative phosphorylation and increased glycolysis. This metabolic reprogramming is probably associated with the IRE1α-dependent expression and stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), an important molecule involved in cell metabolism that sustains the inflammatory profile in B. abortus-infected macrophages. Accordingly, we demonstrated that IRE1α favors the generation of mitochondrial reactive oxygen species (mROS) which has been described as an HIF-1α stabilizing factor. Furthermore, in infected macrophages, IRE1α drives the production of nitric oxide and the release of IL-1β. Collectively, these data unravel a key mechanism linking the UPR and the immunometabolic regulation of macrophages in Brucella infection and highlight IRE1α as a central pathway regulating macrophage metabolic function during infectious diseases.
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spelling pubmed-98426582023-01-18 The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection Guimarães, Erika S. Gomes, Marco Túlio R. Sanches, Rodrigo C. O. Matteucci, Kely Catarine Marinho, Fábio V. Oliveira, Sergio C. Front Immunol Immunology Endoplasmic reticulum (ER) stress plays a major role in several inflammatory disorders. ER stress induces the unfolded protein response (UPR), a conserved response broadly associated with innate immunity and cell metabolic function in various scenarios. Brucella abortus, an intracellular pathogen, triggers the UPR via Stimulator of interferon genes (STING), an important regulator of macrophage metabolism during B. abortus infection. However, whether ER stress pathways underlie macrophage metabolic function during B. abortus infection remains to be elucidated. Here, we showed that the UPR sensor inositol-requiring enzyme 1α (IRE1α) is as an important component regulating macrophage immunometabolic function. In B. abortus infection, IRE1α supports the macrophage inflammatory profile, favoring M1-like macrophages. IRE1α drives the macrophage metabolic reprogramming in infected macrophages, contributing to the reduced oxidative phosphorylation and increased glycolysis. This metabolic reprogramming is probably associated with the IRE1α-dependent expression and stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), an important molecule involved in cell metabolism that sustains the inflammatory profile in B. abortus-infected macrophages. Accordingly, we demonstrated that IRE1α favors the generation of mitochondrial reactive oxygen species (mROS) which has been described as an HIF-1α stabilizing factor. Furthermore, in infected macrophages, IRE1α drives the production of nitric oxide and the release of IL-1β. Collectively, these data unravel a key mechanism linking the UPR and the immunometabolic regulation of macrophages in Brucella infection and highlight IRE1α as a central pathway regulating macrophage metabolic function during infectious diseases. Frontiers Media S.A. 2023-01-03 /pmc/articles/PMC9842658/ /pubmed/36660548 http://dx.doi.org/10.3389/fimmu.2022.1063221 Text en Copyright © 2023 Guimarães, Gomes, Sanches, Matteucci, Marinho and Oliveira 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
Guimarães, Erika S.
Gomes, Marco Túlio R.
Sanches, Rodrigo C. O.
Matteucci, Kely Catarine
Marinho, Fábio V.
Oliveira, Sergio C.
The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection
title The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection
title_full The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection
title_fullStr The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection
title_full_unstemmed The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection
title_short The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during Brucella abortus infection
title_sort endoplasmic reticulum stress sensor ire1α modulates macrophage metabolic function during brucella abortus infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842658/
https://www.ncbi.nlm.nih.gov/pubmed/36660548
http://dx.doi.org/10.3389/fimmu.2022.1063221
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