Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium

Summary: Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens....

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Autores principales:	Jacob Thyrsted, Jacob Storgaard, Julia Blay-Cadanet, Alexander Heinz, Anne Laugaard Thielke, Stefania Crotta, Frank de Paoli, David Olagnier, Andreas Wack, Karsten Hiller, Anne Louise Hansen, Christian Kanstrup Holm
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Immune response Virology Metabolomics Science Q
Acceso en línea:	https://doaj.org/article/4026fa2356d24d3aa8b17fca2a42d3f0
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spelling	oai:doaj.org-article:4026fa2356d24d3aa8b17fca2a42d3f02021-11-20T05:09:38ZInfluenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium2589-004210.1016/j.isci.2021.103300https://doaj.org/article/4026fa2356d24d3aa8b17fca2a42d3f02021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012694https://doaj.org/toc/2589-0042Summary: Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of pseudostratified primary human airway epithelium, we here demonstrate that infection with both IAV and SARS-CoV-2 resulted in distinct metabolic changes including increases in lactate dehydrogenase A (LDHA) expression and LDHA-mediated lactate formation. Interestingly, LDHA regulated both basal and induced mitochondrial anti-viral signaling protein (MAVS)-dependent type I interferon (IFN) responses to promote IAV, but not SARS-CoV-2, replication. Our data demonstrate that LDHA and lactate promote IAV but not SARS-CoV-2 replication by inhibiting MAVS-dependent induction of type I IFN in primary human airway epithelium.Jacob ThyrstedJacob StorgaardJulia Blay-CadanetAlexander HeinzAnne Laugaard ThielkeStefania CrottaFrank de PaoliDavid OlagnierAndreas WackKarsten HillerAnne Louise HansenChristian Kanstrup HolmElsevierarticleImmune responseVirologyMetabolomicsScienceQENiScience, Vol 24, Iss 11, Pp 103300- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immune response Virology Metabolomics Science Q
spellingShingle	Immune response Virology Metabolomics Science Q Jacob Thyrsted Jacob Storgaard Julia Blay-Cadanet Alexander Heinz Anne Laugaard Thielke Stefania Crotta Frank de Paoli David Olagnier Andreas Wack Karsten Hiller Anne Louise Hansen Christian Kanstrup Holm Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium
description	Summary: Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of pseudostratified primary human airway epithelium, we here demonstrate that infection with both IAV and SARS-CoV-2 resulted in distinct metabolic changes including increases in lactate dehydrogenase A (LDHA) expression and LDHA-mediated lactate formation. Interestingly, LDHA regulated both basal and induced mitochondrial anti-viral signaling protein (MAVS)-dependent type I interferon (IFN) responses to promote IAV, but not SARS-CoV-2, replication. Our data demonstrate that LDHA and lactate promote IAV but not SARS-CoV-2 replication by inhibiting MAVS-dependent induction of type I IFN in primary human airway epithelium.
format	article
author	Jacob Thyrsted Jacob Storgaard Julia Blay-Cadanet Alexander Heinz Anne Laugaard Thielke Stefania Crotta Frank de Paoli David Olagnier Andreas Wack Karsten Hiller Anne Louise Hansen Christian Kanstrup Holm
author_facet	Jacob Thyrsted Jacob Storgaard Julia Blay-Cadanet Alexander Heinz Anne Laugaard Thielke Stefania Crotta Frank de Paoli David Olagnier Andreas Wack Karsten Hiller Anne Louise Hansen Christian Kanstrup Holm
author_sort	Jacob Thyrsted
title	Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium
title_short	Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium
title_full	Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium
title_fullStr	Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium
title_full_unstemmed	Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium
title_sort	influenza a induces lactate formation to inhibit type i ifn in primary human airway epithelium
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/4026fa2356d24d3aa8b17fca2a42d3f0
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Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium

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