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dc.contributor.authorLi, Youxian
dc.contributor.authorØsterhus, Stine
dc.contributor.authorJohnsen, Ingvild Bjellmo
dc.date.accessioned2018-09-10T12:09:03Z
dc.date.available2018-09-10T12:09:03Z
dc.date.created2018-05-04T11:04:06Z
dc.date.issued2018
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/11250/2561774
dc.description.abstractHuman cathelicidin antimicriobial peptide (CAMP) is a critical component of host innate immunity with both antimicrobial and immunomodulatory functions. Several pathogens have been shown to downregulate CAMP expression, yet it is unclear if such modulation occurs during a viral infection. In this study, we showed that infection with human metapneumovirus (hMPV), one of the leading causes of respiratory tract infections in young children, strongly suppressed basal and vitamin-D induced CAMP expression in human macrophages. hMPV-mediated suppression of CAMP did not correlate with reduced transcriptional expression of key vitamin D signaling components, such as CYP27B1 or vitamin D receptor, suggesting a vitamin D-independent mechanism. Blocking interferon-signaling pathways did not reverse hMVP-mediated suppression of CAMP, indicating that the suppressive effect is largely interferon-independent. Instead, we identified C/EBPα as the key modulator of hMPV-mediated suppression of CAMP. hMPV infection strongly repressed the expression of C/EBPα, and a knockdown study confirmed that C/EBPα is critical for CAMP expression in human macrophages. Such modulation of CAMP (and C/EBPα) could be reproduced by TLR1/2 ligand treatment in human macrophages, suggesting a common mechanism underlying pathogen-mediated downregulation of CAMP through C/EBPα. This study opens up a new understanding of altered human antimicrobial responses following infections.nb_NO
dc.language.isoengnb_NO
dc.publisherFrontiers Medianb_NO
dc.relation.urihttps://doi.org/10.3389/fimmu.2018.00902
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleHuman Metapneumovirus Infection Inhibits Cathelicidin Antimicrobial Peptide Expression in Human Macrophagesnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.journalFrontiers in Immunologynb_NO
dc.identifier.doihttps://doi.org/10.3389/fimmu.2018.00902
dc.identifier.cristin1583437
dc.description.localcodeCopyright © 2018 Li, Østerhus and Johnsen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).nb_NO
cristin.unitcode194,65,15,0
cristin.unitcode194,66,10,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameInstitutt for biologi
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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