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Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor

Mitochondria regulate steroid hormone synthesis, and in turn sex hormones regulate mitochondrial function for maintaining cellular homeostasis and controlling inflammation. This crosstalk can explain sex differences observed in several pathologies such as in metabolic or inflammatory disorders. Nod-...

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Autores principales: Snäkä, Tiia, Bekkar, Amel, Desponds, Chantal, Prével, Florence, Claudinot, Stéphanie, Isorce, Nathalie, Teixeira, Filipa, Grasset, Coline, Xenarios, Ioannis, Lopez-Mejia, Isabel C., Fajas, Lluis, Fasel, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150262/
https://www.ncbi.nlm.nih.gov/pubmed/35651602
http://dx.doi.org/10.3389/fimmu.2022.882867
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author Snäkä, Tiia
Bekkar, Amel
Desponds, Chantal
Prével, Florence
Claudinot, Stéphanie
Isorce, Nathalie
Teixeira, Filipa
Grasset, Coline
Xenarios, Ioannis
Lopez-Mejia, Isabel C.
Fajas, Lluis
Fasel, Nicolas
author_facet Snäkä, Tiia
Bekkar, Amel
Desponds, Chantal
Prével, Florence
Claudinot, Stéphanie
Isorce, Nathalie
Teixeira, Filipa
Grasset, Coline
Xenarios, Ioannis
Lopez-Mejia, Isabel C.
Fajas, Lluis
Fasel, Nicolas
author_sort Snäkä, Tiia
collection PubMed
description Mitochondria regulate steroid hormone synthesis, and in turn sex hormones regulate mitochondrial function for maintaining cellular homeostasis and controlling inflammation. This crosstalk can explain sex differences observed in several pathologies such as in metabolic or inflammatory disorders. Nod-like receptor X1 (NLRX1) is a mitochondria-associated innate receptor that could modulate metabolic functions and attenuates inflammatory responses. Here, we showed that in an infectious model with the human protozoan parasite, Leishmania guyanensis, NLRX1 attenuated inflammation in females but not in male mice. Analysis of infected female and male bone marrow derived macrophages showed both sex- and genotype-specific differences in both inflammatory and metabolic profiles with increased type I interferon production, mitochondrial respiration, and glycolytic rate in Nlrx1-deficient female BMDMs in comparison to wild-type cells, while no differences were observed between males. Transcriptomics of female and male BMDMs revealed an altered steroid hormone signaling in Nlrx1-deficient cells, and a “masculinization” of Nlrx1-deficient female BMDMs. Thus, our findings suggest that NLRX1 prevents uncontrolled inflammation and metabolism in females and therefore may contribute to the sex differences observed in infectious and inflammatory diseases.
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spelling pubmed-91502622022-05-31 Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor Snäkä, Tiia Bekkar, Amel Desponds, Chantal Prével, Florence Claudinot, Stéphanie Isorce, Nathalie Teixeira, Filipa Grasset, Coline Xenarios, Ioannis Lopez-Mejia, Isabel C. Fajas, Lluis Fasel, Nicolas Front Immunol Immunology Mitochondria regulate steroid hormone synthesis, and in turn sex hormones regulate mitochondrial function for maintaining cellular homeostasis and controlling inflammation. This crosstalk can explain sex differences observed in several pathologies such as in metabolic or inflammatory disorders. Nod-like receptor X1 (NLRX1) is a mitochondria-associated innate receptor that could modulate metabolic functions and attenuates inflammatory responses. Here, we showed that in an infectious model with the human protozoan parasite, Leishmania guyanensis, NLRX1 attenuated inflammation in females but not in male mice. Analysis of infected female and male bone marrow derived macrophages showed both sex- and genotype-specific differences in both inflammatory and metabolic profiles with increased type I interferon production, mitochondrial respiration, and glycolytic rate in Nlrx1-deficient female BMDMs in comparison to wild-type cells, while no differences were observed between males. Transcriptomics of female and male BMDMs revealed an altered steroid hormone signaling in Nlrx1-deficient cells, and a “masculinization” of Nlrx1-deficient female BMDMs. Thus, our findings suggest that NLRX1 prevents uncontrolled inflammation and metabolism in females and therefore may contribute to the sex differences observed in infectious and inflammatory diseases. Frontiers Media S.A. 2022-05-16 /pmc/articles/PMC9150262/ /pubmed/35651602 http://dx.doi.org/10.3389/fimmu.2022.882867 Text en Copyright © 2022 Snäkä, Bekkar, Desponds, Prével, Claudinot, Isorce, Teixeira, Grasset, Xenarios, Lopez-Mejia, Fajas and Fasel 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
Snäkä, Tiia
Bekkar, Amel
Desponds, Chantal
Prével, Florence
Claudinot, Stéphanie
Isorce, Nathalie
Teixeira, Filipa
Grasset, Coline
Xenarios, Ioannis
Lopez-Mejia, Isabel C.
Fajas, Lluis
Fasel, Nicolas
Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor
title Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor
title_full Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor
title_fullStr Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor
title_full_unstemmed Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor
title_short Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor
title_sort sex-biased control of inflammation and metabolism by a mitochondrial nod-like receptor
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150262/
https://www.ncbi.nlm.nih.gov/pubmed/35651602
http://dx.doi.org/10.3389/fimmu.2022.882867
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