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dc.contributor.authorUeland, Thor
dc.contributor.authorAstrup, Elisabeth
dc.contributor.authorOtterdal, Kari
dc.contributor.authorLekva, Tove
dc.contributor.authorJanardhanan, Jeshina
dc.contributor.authorPrakash, John A.
dc.contributor.authorThomas, Kurien
dc.contributor.authorMichelsen, Annika
dc.contributor.authorAukrust, Pål
dc.contributor.authorVarghese, George M.
dc.contributor.authorDamås, Jan Kristian
dc.date.accessioned2021-06-28T12:56:30Z
dc.date.available2021-06-28T12:56:30Z
dc.date.issued2021-04-29
dc.description.abstractBackground - The mechanisms that control local and systemic inflammation in scrub typhus have only been partially elucidated. The wingless (Wnt) signaling pathways are emerging as important regulators of inflammation and infection, but have not been investigated in scrub typhus. <p> <p>Methodology/Principal findings - Plasma levels of secreted Wnt antagonists (i.e. DKK-1, sFRP-3, WIF-1 and SOST) were analyzed in patients with scrub typhus (n = 129), patients with similar febrile illness without O. tsutsugamushi infection (n = 31), febrile infectious disease controls, and in healthy controls (n = 31) from the same area of South India, and were correlated to markers of inflammation, immune and endothelial cell activation as well as for their association with organ specific dysfunction and mortality in these patients. We found i) Levels of SOST and in particular sFRP-3 and WIF-1 were markedly increased and DKK-1 decreased in scrub typhus patients at admission to the hospital compared to healthy controls. ii) In recovering scrub typhus patients, SOST, sFRP-3 and WIF-1 decreased and DKK-1 increased. iii) SOST was positively correlated with markers of monocyte/macrophage and endothelial/vascular activation as well as with renal dysfunction and poor outcome iv) Finally, regulation of Wnt pathways by O. tsutsugamushi in vitro in monocytes and ex vivo in mononuclear cells isolated from patients with scrub typhus, as evaluated by gene expression studies available in public repositories, revealed markedly attenuated canonical Wnt signaling. <p> <p>Conclusions/Significance - Our findings suggest that scrub typhus is characterized by attenuated Wnt signaling possibly involving dysregulated levels of several secreted pathway antagonists. The secreted Wnt antagonist SOST was strongly associated with renal dysfunction and poor prognosis in these patients.en_US
dc.identifier.citationUeland, Astrup, Otterdal, Lekva, Janardhanan, Prakash, Thomas, Michelsen, Aukrust, Varghese, Damås. Secreted wnt antagonists in scrub typhus. PLoS Neglected Tropical Diseases. 2021;15(4)en_US
dc.identifier.cristinIDFRIDAID 1917912
dc.identifier.doi10.1371/journal.pntd.0009185
dc.identifier.issn1935-2727
dc.identifier.issn1935-2735
dc.identifier.urihttps://hdl.handle.net/10037/21589
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLoS Neglected Tropical Diseases
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/?/196403/?/?/?/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleSecreted wnt antagonists in scrub typhusen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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