Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection

Myeloid-derived suppressor cells (MDSCs) are a compendium of immature myeloid cells that exhibit potent T-cell suppressive capacity and expand during pathological conditions such as cancer and chronic infections. Although well-characterized in cancer, the physiology of MDSCs in the infection setting...

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Autores principales:	Oliver Dietrich, Alexander Heinz, Oliver Goldmann, Robert Geffers, Andreas Beineke, Karsten Hiller, Antoine-Emmanuel Saliba, Eva Medina
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	myeloid-derived suppressor cells staphylococcus aureus immunometabolism single-cell rna sequencing Medicine R Internal medicine RC31-1245
Acceso en línea:	https://doaj.org/article/89060c0cd6114c16a5b9cd6c9fb82f8f
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spelling	oai:doaj.org-article:89060c0cd6114c16a5b9cd6c9fb82f8f2021-12-02T12:40:22ZDysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection1662-811X1662-812810.1159/000519306https://doaj.org/article/89060c0cd6114c16a5b9cd6c9fb82f8f2021-11-01T00:00:00Zhttps://www.karger.com/Article/FullText/519306https://doaj.org/toc/1662-811Xhttps://doaj.org/toc/1662-8128Myeloid-derived suppressor cells (MDSCs) are a compendium of immature myeloid cells that exhibit potent T-cell suppressive capacity and expand during pathological conditions such as cancer and chronic infections. Although well-characterized in cancer, the physiology of MDSCs in the infection setting remains enigmatic. Here, we integrated single-cell RNA sequencing (scRNA-seq) and functional metabolic profiling to gain deeper insights into the factors governing the generation and maintenance of MDSCs in chronic Staphylococcus aureus infection. We found that MDSCs originate not only in the bone marrow but also at extramedullary sites in S. aureus-infected mice. scRNA-seq showed that infection-driven MDSCs encompass a spectrum of myeloid precursors in different stages of differentiation, ranging from promyelocytes to mature neutrophils. Furthermore, the scRNA-seq analysis has also uncovered valuable phenotypic markers to distinguish mature myeloid cells from immature MDSCs. Metabolic profiling indicates that MDSCs exhibit high glycolytic activity and high glucose consumption rates, which are required for undergoing terminal maturation. However, rapid glucose consumption by MDSCs added to infection-induced perturbations in the glucose supplies in infected mice hinders the terminal maturation of MDSCs and promotes their accumulation in an immature stage. In a proof-of-concept in vivo experiment, we demonstrate the beneficial effect of increasing glucose availability in promoting MDSC terminal differentiation in infected mice. Our results provide valuable information of how metabolic alterations induced by infection influence reprogramming and differentiation of MDSCs.Oliver DietrichAlexander HeinzOliver GoldmannRobert GeffersAndreas BeinekeKarsten HillerAntoine-Emmanuel SalibaEva MedinaKarger Publishersarticlemyeloid-derived suppressor cellsstaphylococcus aureusimmunometabolismsingle-cell rna sequencingMedicineRInternal medicineRC31-1245ENJournal of Innate Immunity, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myeloid-derived suppressor cells staphylococcus aureus immunometabolism single-cell rna sequencing Medicine R Internal medicine RC31-1245
spellingShingle	myeloid-derived suppressor cells staphylococcus aureus immunometabolism single-cell rna sequencing Medicine R Internal medicine RC31-1245 Oliver Dietrich Alexander Heinz Oliver Goldmann Robert Geffers Andreas Beineke Karsten Hiller Antoine-Emmanuel Saliba Eva Medina Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection
description	Myeloid-derived suppressor cells (MDSCs) are a compendium of immature myeloid cells that exhibit potent T-cell suppressive capacity and expand during pathological conditions such as cancer and chronic infections. Although well-characterized in cancer, the physiology of MDSCs in the infection setting remains enigmatic. Here, we integrated single-cell RNA sequencing (scRNA-seq) and functional metabolic profiling to gain deeper insights into the factors governing the generation and maintenance of MDSCs in chronic Staphylococcus aureus infection. We found that MDSCs originate not only in the bone marrow but also at extramedullary sites in S. aureus-infected mice. scRNA-seq showed that infection-driven MDSCs encompass a spectrum of myeloid precursors in different stages of differentiation, ranging from promyelocytes to mature neutrophils. Furthermore, the scRNA-seq analysis has also uncovered valuable phenotypic markers to distinguish mature myeloid cells from immature MDSCs. Metabolic profiling indicates that MDSCs exhibit high glycolytic activity and high glucose consumption rates, which are required for undergoing terminal maturation. However, rapid glucose consumption by MDSCs added to infection-induced perturbations in the glucose supplies in infected mice hinders the terminal maturation of MDSCs and promotes their accumulation in an immature stage. In a proof-of-concept in vivo experiment, we demonstrate the beneficial effect of increasing glucose availability in promoting MDSC terminal differentiation in infected mice. Our results provide valuable information of how metabolic alterations induced by infection influence reprogramming and differentiation of MDSCs.
format	article
author	Oliver Dietrich Alexander Heinz Oliver Goldmann Robert Geffers Andreas Beineke Karsten Hiller Antoine-Emmanuel Saliba Eva Medina
author_facet	Oliver Dietrich Alexander Heinz Oliver Goldmann Robert Geffers Andreas Beineke Karsten Hiller Antoine-Emmanuel Saliba Eva Medina
author_sort	Oliver Dietrich
title	Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection
title_short	Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection
title_full	Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection
title_fullStr	Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection
title_full_unstemmed	Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection
title_sort	dysregulated immunometabolism is associated with the generation of myeloid-derived suppressor cells in staphylococcus aureus chronic infection
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/89060c0cd6114c16a5b9cd6c9fb82f8f
work_keys_str_mv	AT oliverdietrich dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection AT alexanderheinz dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection AT olivergoldmann dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection AT robertgeffers dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection AT andreasbeineke dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection AT karstenhiller dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection AT antoineemmanuelsaliba dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection AT evamedina dysregulatedimmunometabolismisassociatedwiththegenerationofmyeloidderivedsuppressorcellsinstaphylococcusaureuschronicinfection
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Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection

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