Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.

Regulation of cellular metabolism is now recognized as a crucial mechanism for the activation of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, path...

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Autores principales:	Saray Gutiérrez, Julia Fischer, Raja Ganesan, Nina Judith Hos, Gökhan Cildir, Martina Wolke, Alberto Pessia, Peter Frommolt, Vincenzo Desiderio, Vidya Velagapudi, Nirmal Robinson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b990dc2fb1bd4d26bb009ef804bbfd30
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spelling	oai:doaj.org-article:b990dc2fb1bd4d26bb009ef804bbfd302021-12-02T20:00:06ZSalmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.1553-73661553-737410.1371/journal.ppat.1009943https://doaj.org/article/b990dc2fb1bd4d26bb009ef804bbfd302021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009943https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Regulation of cellular metabolism is now recognized as a crucial mechanism for the activation of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. Despite this dynamic interplay in host-pathogen interactions, the role of immunometabolism in the context of intracellular bacterial infections is still unclear. Here, employing unbiased metabolomic and transcriptomic approaches, we investigated the role of metabolic adaptations of macrophages upon Salmonella enterica serovar Typhimurium (S. Typhimurium) infections. Importantly, our results suggest that S. Typhimurium abrogates glycolysis and its modulators such as insulin-signaling to impair macrophage defense. Mechanistically, glycolysis facilitates glycolytic enzyme aldolase A mediated v-ATPase assembly and the acidification of phagosomes which is critical for lysosomal degradation. Thus, impairment in the glycolytic machinery eventually leads to decreased bacterial clearance and antigen presentation in murine macrophages (BMDM). Collectively, our results highlight a vital molecular link between metabolic adaptation and phagosome maturation in macrophages, which is targeted by S. Typhimurium to evade cell-autonomous defense.Saray GutiérrezJulia FischerRaja GanesanNina Judith HosGökhan CildirMartina WolkeAlberto PessiaPeter FrommoltVincenzo DesiderioVidya VelagapudiNirmal RobinsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009943 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Saray Gutiérrez Julia Fischer Raja Ganesan Nina Judith Hos Gökhan Cildir Martina Wolke Alberto Pessia Peter Frommolt Vincenzo Desiderio Vidya Velagapudi Nirmal Robinson Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.
description	Regulation of cellular metabolism is now recognized as a crucial mechanism for the activation of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. Despite this dynamic interplay in host-pathogen interactions, the role of immunometabolism in the context of intracellular bacterial infections is still unclear. Here, employing unbiased metabolomic and transcriptomic approaches, we investigated the role of metabolic adaptations of macrophages upon Salmonella enterica serovar Typhimurium (S. Typhimurium) infections. Importantly, our results suggest that S. Typhimurium abrogates glycolysis and its modulators such as insulin-signaling to impair macrophage defense. Mechanistically, glycolysis facilitates glycolytic enzyme aldolase A mediated v-ATPase assembly and the acidification of phagosomes which is critical for lysosomal degradation. Thus, impairment in the glycolytic machinery eventually leads to decreased bacterial clearance and antigen presentation in murine macrophages (BMDM). Collectively, our results highlight a vital molecular link between metabolic adaptation and phagosome maturation in macrophages, which is targeted by S. Typhimurium to evade cell-autonomous defense.
format	article
author	Saray Gutiérrez Julia Fischer Raja Ganesan Nina Judith Hos Gökhan Cildir Martina Wolke Alberto Pessia Peter Frommolt Vincenzo Desiderio Vidya Velagapudi Nirmal Robinson
author_facet	Saray Gutiérrez Julia Fischer Raja Ganesan Nina Judith Hos Gökhan Cildir Martina Wolke Alberto Pessia Peter Frommolt Vincenzo Desiderio Vidya Velagapudi Nirmal Robinson
author_sort	Saray Gutiérrez
title	Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.
title_short	Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.
title_full	Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.
title_fullStr	Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.
title_full_unstemmed	Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.
title_sort	salmonella typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b990dc2fb1bd4d26bb009ef804bbfd30
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Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.

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