dc.contributor.author | Li, Youxian | |
dc.contributor.author | Østerhus, Stine | |
dc.contributor.author | Johnsen, Ingvild Bjellmo | |
dc.date.accessioned | 2018-09-10T12:09:03Z | |
dc.date.available | 2018-09-10T12:09:03Z | |
dc.date.created | 2018-05-04T11:04:06Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 1664-3224 | |
dc.identifier.uri | http://hdl.handle.net/11250/2561774 | |
dc.description.abstract | Human 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.iso | eng | nb_NO |
dc.publisher | Frontiers Media | nb_NO |
dc.relation.uri | https://doi.org/10.3389/fimmu.2018.00902 | |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Human Metapneumovirus Infection Inhibits Cathelicidin Antimicrobial Peptide Expression in Human Macrophages | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | publishedVersion | nb_NO |
dc.source.journal | Frontiers in Immunology | nb_NO |
dc.identifier.doi | https://doi.org/10.3389/fimmu.2018.00902 | |
dc.identifier.cristin | 1583437 | |
dc.description.localcode | Copyright © 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.unitcode | 194,65,15,0 | |
cristin.unitcode | 194,66,10,0 | |
cristin.unitname | Institutt for klinisk og molekylær medisin | |
cristin.unitname | Institutt for biologi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |