{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:36:41Z","timestamp":1789094201679,"version":"build-2803163510"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>HIF1\u03b1 is an important transcription factor regulating not only cellular responses to hypoxia, but also anti-infective defense responses. We recently showed that HIF1\u03b1 hampers replication of the obligate intracellular pathogen <jats:italic>Coxiella burnetii<\/jats:italic> 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 HIF1\u03b1 and\/or hypoxia might be involved in the induction of <jats:italic>C. burnetii<\/jats:italic> persistence, we analyzed the role of HIF1\u03b1 and hypoxia in the interaction of macrophages with <jats:italic>C. burnetii<\/jats:italic> to understand how the bacteria manipulate HIF1\u03b1 stability and activity. We demonstrate that a <jats:italic>C. burnetii<\/jats:italic>-infection initially induces HIF1\u03b1 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 HIF1\u03b1 destabilization have been identified, our results demonstrate that <jats:italic>C. burnetii<\/jats:italic> influences the expression of HIF1\u03b1 target genes in multiple ways. Therefore, a <jats:italic>C. burnetii<\/jats:italic> infection promotes HIF1\u03b1-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, <jats:italic>C. burnetii<\/jats:italic> modulates HIF1\u03b1 in a still elusive manner and alters the expression of multiple HIF1\u03b1 target genes.<\/jats:p>","DOI":"10.3389\/fcimb.2022.867689","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T05:19:49Z","timestamp":1654751989000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Coxiella burnetii Affects HIF1\u03b1 Accumulation and HIF1\u03b1 Target Gene Expression"],"prefix":"10.3389","volume":"12","author":[{"given":"Inaya","family":"Hayek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Szperlinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"L\u00fchrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.3390\/ijms18122509","article-title":"Coxiella burnetii Lipopolysaccharide: What Do We Know?","volume":"18","author":"Abnave","year":"2017","journal-title":"Int. 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