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AuthorZenk, Sebastian F.dc.contributor.author
AuthorHauck, Sebastiandc.contributor.author
AuthorMayer, Danieldc.contributor.author
AuthorGrieshober, Markdc.contributor.author
AuthorStenger, Steffendc.contributor.author
Date of accession2021-06-10T12:46:19Zdc.date.accessioned
Available in OPARU since2021-06-10T12:46:19Zdc.date.available
Date of first publication2021-06-02dc.date.issued
AbstractHypoxia-inducible factor (HIF) is a key oxygen sensor that controls gene expression patterns to adapt cellular metabolism to hypoxia. Pharmacological inhibition of prolylhydroxylases stabilizes HIFs and mimics hypoxia, leading to increased expression of more than 300 genes. Whether the genetic program initialized by HIFs affects immune responses against microbial pathogens, is not well studied. Recently we showed that hypoxia enhances antimicrobial activity against Mycobacterium tuberculosis (Mtb) in human macrophages. The objective of this study was to evaluate whether the oxygen sensor HIF is involved in hypoxia-mediated antimycobacterial activity. Treatment of Mtbinfected macrophages with the prolyl-hydroxylase inhibitor Molidustat reduced the release of TNFa and IL-10, two key cytokines involved in the immune response in tuberculosis. Molidustat also interferes with the p38 MAP kinase pathway. HIF-stabilization by Molidustat also induced the upregulation of the Vitamin D receptor and human b defensin 2, which define an antimicrobial effector pathway in human macrophages. Consequently, these immunological effects resulted in reduced proliferation of virulent Mtb in human macrophages. Therefore, HIFs may be attractive new candidates for hostdirected therapies against infectious diseases caused by intracellular bacteria, including tuberculosis.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY 4.0 Internationaldc.rights
Link to license texthttps://creativecommons.org/licenses/by/4.0/dc.rights.uri
KeywordHIFdc.subject
KeywordHumandc.subject
KeywordMolidustatdc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHTuberculosisdc.subject.mesh
MeSHHypoxiadc.subject.mesh
MeSHMacrophagesdc.subject.mesh
TitleStabilization of hypoxia-inducible factor promotes antimicrobial activity of human macrophages against mycobacterium tuberculosisdc.title
Resource typeWissenschaftlicher Artikeldc.type
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-38005dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-38067-4dc.identifier.urn
GNDTuberkulosedc.subject.gnd
GNDHypoxie-induzierbarer Faktordc.subject.gnd
GNDMakrophagedc.subject.gnd
InstitutionUKU. Institut für Medizinische Mikrobiologie und Hygieneuulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
DOI of original publication10.3389/fimmu.2021.678354dc.relation1.doi
Source - Title of sourceFrontiers in Immunologysource.title
Source - Place of publicationFrontiers Mediasource.publisher
Source - Volume12source.volume
Source - Year2021source.year
Source - Article number678354source.articleNumber
Source - eISSN1664-3224source.identifier.eissn
FundingFörderprogramm Biotechnologie / Baden-Württemberg Stiftunguulm.funding
FundingSFB 1279: Exploiting the Human Peptidome for Novel Antimicrobial and Anticancer Agents / DFG [316249678; STE 925/4-1]uulm.funding
University Bibliographyjauulm.unibibliographie


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Except where otherwise noted, this item's license is described as CC BY 4.0 International