{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:03:22Z","timestamp":1790427802568,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Staphylococcus aureus may cause serious infections and is one of the most lethal and common causes of sepsis. TLR2 has been described as the main pattern recognition receptor that senses S. aureus and elicits production of proinflammatory cytokines via MyD88\u2013NF-\u03baB signaling. S. aureus can also induce the production of IFN-\u03b2, a cytokine that requires IFN regulatory factors (IRFs) for its transcription, but the signaling mechanism for IFN-\u03b2 induction by S. aureus are unclear. Surprisingly, we demonstrate that activation of TLR2 by lipoproteins does not contribute to IFN-\u03b2 production but instead can suppress the induction of IFN-\u03b2 in human primary monocytes and monocyte-derived macrophages. The production of IFN-\u03b2 was induced by TLR8-mediated sensing of S. aureus RNA, which triggered IRF5 nuclear accumulation, and this could be antagonized by concomitant TLR2 signaling. The TLR8-mediated activation of IRF5 was dependent on TAK1 and I\u03baB kinase (IKK)\u03b2, which thus reveals a physiological role of the recently described IRF5-activating function of IKK\u03b2. TLR8\u2013IRF5 signaling was necessary for induction of IFN-\u03b2 and IL-12 by S. aureus, and it also contributed to the induction of TNF. In conclusion, our study demonstrates a physiological role of TLR8 in the sensing of entire S. aureus in human primary phagocytes, including the induction of IFN-\u03b2 and IL-12 production via a TAK1\u2013IKK\u03b2\u2013IRF5 pathway that can be inhibited by TLR2 signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.1403176","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T02:46:57Z","timestamp":1434595617000},"page":"1100-1111","source":"Crossref","is-referenced-by-count":126,"title":["TLR8 Senses <i>Staphylococcus aureus<\/i> RNA in Human Primary Monocytes and Macrophages and Induces IFN-\u03b2 Production via a TAK1\u2013IKK\u03b2\u2013IRF5 Signaling Pathway"],"prefix":"10.1093","volume":"195","author":[{"given":"Bjarte","family":"Bergstr\u00f8m","sequence":"first","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie H","family":"Aune","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A","family":"Awuh","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June F","family":"Kojen","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjetil J","family":"Blix","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liv","family":"Ryan","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trude H","family":"Flo","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom E","family":"Mollnes","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]},{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet , Oslo N-0027 ,","place":["Norway"]},{"name":"K.G. Jebsen Inflammation Research Center, University of Oslo , Oslo N-0027 ,","place":["Norway"]},{"name":"Research Laboratory, Nordland Hospital , Bod\u00f8 N-8092 ,","place":["Norway"]},{"name":"Institute of Clinical Medicine, University of Troms\u00f8 , Troms\u00f8 N-9037 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje","family":"Espevik","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-9258","authenticated-orcid":false,"given":"J\u00f8rgen","family":"Stenvik","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim N-7491 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703581672800_r1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1365-2249.2009.03950.x","article-title":"The rise and rise of Staphylococcus aureus: laughing in the face of granulocytes","volume":"157","author":"Anwar","year":"2009","journal-title":"Clin. 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