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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-...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9150262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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