{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:23:28Z","timestamp":1792513408603,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T00:00:00Z","timestamp":1477267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2016,12]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Malaria elicits inflammatory responses, which, if not well regulated, may exert detrimental effects. When activated, triggering receptor expressed on myeloid cells 1 (TREM<\/jats:styled-content>\u20101) enhances inflammatory responses by increasing secretion of IL<\/jats:styled-content>\u20108 and other Th1 cytokines. In contrast, TREM<\/jats:styled-content>\u2010like transcript 1 (TREML<\/jats:styled-content>\u20101) promotes anti\u2010inflammatory responses by binding to TREM<\/jats:styled-content>\u20101 ligands and competing with TREM<\/jats:styled-content>\u20101, thus antagonizing TREM<\/jats:styled-content>\u20101 activation to reduce inflammation. Endothelial protein C receptor (EPCR<\/jats:styled-content>) also mediates anti\u2010inflammatory responses by activating endothelial protein C (PC<\/jats:styled-content>). Upon microbial stimulation, soluble forms of TREM<\/jats:styled-content>\u20101 (sTREM<\/jats:styled-content>\u20101) and soluble EPCR<\/jats:styled-content> (sEPCR<\/jats:styled-content>) are released. Their plasma levels reflect the degree of inflammation and the severity of infection.<\/jats:p><\/jats:sec>Methods<\/jats:title>In a cross\u2010sectional study comparing patients with severe with uncomplicated malaria, sTREM<\/jats:styled-content>\u20101, soluble TREML<\/jats:styled-content>\u20101 (sTREML<\/jats:styled-content>\u20101) and sEPCR<\/jats:styled-content> plasma levels as well as plasma levels of sEPCR<\/jats:styled-content> derived from convalescent patients were quantified. Samples were collected on admittance of paediatric patients infected with Plasmodium falciparum<\/jats:italic> to hospitals in Accra, Ghana. Distinct genetic regions of the genes encoding TREM<\/jats:styled-content>\u20101, EPCR<\/jats:styled-content>, interleukin (IL<\/jats:styled-content>)\u20108 and IL<\/jats:styled-content>\u201018 encompassing known genetic polymorphisms that influence plasma levels underwent DNA<\/jats:styled-content> sequencing.<\/jats:p><\/jats:sec>Results<\/jats:title>Higher sTREM<\/jats:styled-content>\u20101 levels were observed among children suffering from severe malaria compared to those with uncomplicated malaria (P<\/jats:italic> = 0.049). Low TREM<\/jats:styled-content>\u20101 to TREML<\/jats:styled-content>\u20101 ratios were associated with uncomplicated malaria (P<\/jats:italic> = 0.033). The TREM<\/jats:styled-content>1<\/jats:italic> rs2234237T variant causing the amino acid exchange Thr25Ser, which has been associated with higher TREM<\/jats:styled-content>\u20101 plasma levels, was significantly more frequent among patients with severe malaria than in those with uncomplicated malaria (P<\/jats:italic> = 0.036). Low levels of sEPCR<\/jats:styled-content> were observed in severe and uncomplicated malaria, while variant genotypes of IL<\/jats:styled-content>8, IL<\/jats:styled-content>18<\/jats:italic> and EPCR<\/jats:styled-content><\/jats:italic> did not show any association.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Higher plasma levels of sTREM<\/jats:styled-content>\u20101 alone or relative to sTREML<\/jats:styled-content>\u20101 during malaria predispose to the phenotype of severe malaria. Carriage of the TREM<\/jats:styled-content>1<\/jats:italic> rs2234237T allele appears to be a risk factor for the development of severe malaria.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tmi.12787","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T09:18:45Z","timestamp":1474967925000},"page":"1592-1601","source":"Crossref","is-referenced-by-count":24,"title":["Triggering receptor expressed on myeloid cells 1 (TREM<\/scp>\u20101) and cytokine gene variants in complicated and uncomplicated malaria"],"prefix":"10.1111","volume":"21","author":[{"given":"Selorme","family":"Adukpo","sequence":"first","affiliation":[{"name":"Institute of Tropical Medicine University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"Immunology Department Noguchi Memorial Institute for Medical Research College of Health Sciences University of Ghana Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben 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