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dc.contributor.authorEhrnstrøm, Birgitta
dc.contributor.authorKojen, June Frengen
dc.contributor.authorGiambelluca, Miriam
dc.contributor.authorRyan, Liv
dc.contributor.authorMoen, Siv Helen
dc.contributor.authorHu, Zhenyi
dc.contributor.authorYin, Hang
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorDamås, Jan Kristian
dc.contributor.authorEspevik, Terje
dc.contributor.authorStenvik, Jørgen
dc.identifier.citationJournal of Leukocyte Biology. 2020, .nb_NO
dc.description.abstractWe recently showed that TLR8 is critical for the detection of Gram‐positive bacteria by human monocytes. Here, we hypothesized that TLR8 and complement together regulate antibacterial responses in human blood. Anticoagulated blood was treated with selective inhibitors of TLR8 and/or complement C5, and then challenged with live Streptococcus agalactiae (Group B streptococcus, GBS), Staphylococcus aureus, or Escherichia coli. Cytokine production, plasma membrane permeability, bacterial survival, phagocytosis, and activation of coagulation was examined. GBS and S. aureus, but not E. coli, triggered TLR8‐dependent production of IL‐12p70, IL‐1β, TNF, and IL‐6 in fresh human whole blood. In purified polymorphonuclear neutrophils (PMN), GBS and S. aureus induced IL‐8 release in part via TLR8, whereas PMN plasma membrane leakage and extracellular DNA levels increased independently of TLR8. TLR8 was more important than C5 for bacteria‐induced production of IL‐12p70, IL‐1β, and TNF in blood, whereas IL‐8 release was more C5 dependent. Both TLR8 and C5 induced IL‐6 release and activation of prothrombin cleavage, and here their combined effects were additive. Blocking of C5 or C5aR1 attenuated phagocytosis and increased the extracellular growth of GBS in blood, whereas TLR8 inhibition neither reduced phagocytosis nor intracellular killing of GBS and S. aureus. In conclusion, TLR8 is more important than C5 for production of IL‐12p70, IL‐1β, and TNF upon GBS and S. aureus infection in blood, whereas C5 is central for IL‐8 release and phagocytosis. Both TLR8 and C5 mediate IL‐6 release and activation of coagulation during challenge with Gram‐positive bacteria in blood.nb_NO
dc.publisherJohn Wiley & Sonsnb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleTLR8 and complement C5 induce cytokine release and thrombin activation in human whole blood challenged with Gram-positive bacterianb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalJournal of Leukocyte Biologynb_NO
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.relation.projectSamarbeidsorganet mellom Helse Midt-Norge og NTNU: 90162400nb_NO
dc.description.localcode© 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.nb_NO
cristin.unitnameInstitutt for klinisk og molekylær medisin

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