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Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression

HIF1α is an important transcription factor regulating not only cellular responses to hypoxia, but also anti-infective defense responses. We recently showed that HIF1α hampers replication of the obligate intracellular pathogen Coxiella burnetii which causes the zoonotic disease Q fever. Prior to deve...

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Autores principales: Hayek, Inaya, Szperlinski, Manuela, Lührmann, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218251/
https://www.ncbi.nlm.nih.gov/pubmed/35755850
http://dx.doi.org/10.3389/fcimb.2022.867689
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author Hayek, Inaya
Szperlinski, Manuela
Lührmann, Anja
author_facet Hayek, Inaya
Szperlinski, Manuela
Lührmann, Anja
author_sort Hayek, Inaya
collection PubMed
description HIF1α is an important transcription factor regulating not only cellular responses to hypoxia, but also anti-infective defense responses. We recently showed that HIF1α hampers replication of the obligate intracellular pathogen Coxiella burnetii which causes the zoonotic disease Q fever. Prior to development of chronic Q fever, it is assumed that the bacteria enter a persistent state. As HIF1α and/or hypoxia might be involved in the induction of C. burnetii persistence, we analyzed the role of HIF1α and hypoxia in the interaction of macrophages with C. burnetii to understand how the bacteria manipulate HIF1α stability and activity. We demonstrate that a C. burnetii-infection initially induces HIF1α stabilization, which decreases then over the course of an infection. This reduction depends on bacterial viability and a functional type IV secretion system (T4SS). While neither the responsible T4SS effector protein(s) nor the molecular mechanism leading to this partial HIF1α destabilization have been identified, our results demonstrate that C. burnetii influences the expression of HIF1α target genes in multiple ways. Therefore, a C. burnetii infection promotes HIF1α-mediated upregulation of several metabolic target genes; affects apoptosis-regulators towards a more pro-apoptotic signature; and under hypoxic conditions, shifts the ratio of the inflammatory genes analyzed towards a pro-inflammatory profile. Taken together, C. burnetii modulates HIF1α in a still elusive manner and alters the expression of multiple HIF1α target genes.
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spelling pubmed-92182512022-06-24 Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression Hayek, Inaya Szperlinski, Manuela Lührmann, Anja Front Cell Infect Microbiol Cellular and Infection Microbiology HIF1α is an important transcription factor regulating not only cellular responses to hypoxia, but also anti-infective defense responses. We recently showed that HIF1α hampers replication of the obligate intracellular pathogen Coxiella burnetii which causes the zoonotic disease Q fever. Prior to development of chronic Q fever, it is assumed that the bacteria enter a persistent state. As HIF1α and/or hypoxia might be involved in the induction of C. burnetii persistence, we analyzed the role of HIF1α and hypoxia in the interaction of macrophages with C. burnetii to understand how the bacteria manipulate HIF1α stability and activity. We demonstrate that a C. burnetii-infection initially induces HIF1α stabilization, which decreases then over the course of an infection. This reduction depends on bacterial viability and a functional type IV secretion system (T4SS). While neither the responsible T4SS effector protein(s) nor the molecular mechanism leading to this partial HIF1α destabilization have been identified, our results demonstrate that C. burnetii influences the expression of HIF1α target genes in multiple ways. Therefore, a C. burnetii infection promotes HIF1α-mediated upregulation of several metabolic target genes; affects apoptosis-regulators towards a more pro-apoptotic signature; and under hypoxic conditions, shifts the ratio of the inflammatory genes analyzed towards a pro-inflammatory profile. Taken together, C. burnetii modulates HIF1α in a still elusive manner and alters the expression of multiple HIF1α target genes. Frontiers Media S.A. 2022-06-09 /pmc/articles/PMC9218251/ /pubmed/35755850 http://dx.doi.org/10.3389/fcimb.2022.867689 Text en Copyright © 2022 Hayek, Szperlinski and Lührmann 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 Cellular and Infection Microbiology
Hayek, Inaya
Szperlinski, Manuela
Lührmann, Anja
Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression
title Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression
title_full Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression
title_fullStr Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression
title_full_unstemmed Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression
title_short Coxiella burnetii Affects HIF1α Accumulation and HIF1α Target Gene Expression
title_sort coxiella burnetii affects hif1α accumulation and hif1α target gene expression
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218251/
https://www.ncbi.nlm.nih.gov/pubmed/35755850
http://dx.doi.org/10.3389/fcimb.2022.867689
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