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The molecular pathways that account for these effects and the capacity of CPMV to activate human cells are not well defined. Here, we examine the ability of CPMV particles to activate human monocytes, dendritic cells (DCs) and macrophages. Monocytes in peripheral blood mononuclear cell cultures and purified CD14+ monocytes were readily activated by CPMV <jats:italic>in vitro<\/jats:italic>, leading to induction of HLA\u2010DR, CD86, PD\u2010L1, IL\u201015R and CXCL10 expression. Monocytes released chemokines, CXCL10, MIP\u20101\u03b1 and MIP\u20101\u03b2 into cell culture supernatants after incubation with CPMV. DC subsets (pDC and mDC) and monocyte\u2010derived\u00a0macrophages also demonstrated evidence of activation after incubation with CPMV. Inhibitors of spleen tyrosine kinase (SYK), endocytosis or endocytic acidification impaired the capacity of CPMV to activate monocytes. Furthermore, CPMV activation of monocytes was partially blocked by a TLR7\/8 antagonist. These data demonstrate that CPMV activates human monocytes in a manner dependent on SYK signalling, endosomal acidification and with an important contribution from TLR7\/8 recognition.<\/jats:p>","DOI":"10.1111\/imm.13135","type":"journal-article","created":{"date-parts":[[2019,10,20]],"date-time":"2019-10-20T16:38:40Z","timestamp":1571589520000},"page":"183-192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Endosomal toll\u2010like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus"],"prefix":"10.1111","volume":"159","author":[{"given":"Marwah M.","family":"Albakri","sequence":"first","affiliation":[{"name":"Department of Pathology School of Medicine Case Western Reserve University Cleveland OH USA"},{"name":"Department of Medical Laboratory Technology College of Applied Medical Sciences Taibah University Medina Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Veliz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering School of Medicine Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven N.","family":"Fiering","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth Norris Cotton Cancer Center Lebanon NH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole F.","family":"Steinmetz","sequence":"additional","affiliation":[{"name":"Department of NanoEngineering University of California San Diego La Jolla CA USA"},{"name":"Department of Radiology University of California San Diego La Jolla CA USA"},{"name":"Department of Bioengineering University of California San Diego La Jolla CA USA"},{"name":"Moores Cancer Center University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-8682","authenticated-orcid":false,"given":"Scott F.","family":"Sieg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and HIV Medicine School of Medicine Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000150478"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.5b00344"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc0402888"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1368"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.201900003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040515"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00126"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.5b04877"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6107(91)90003-B"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.08.023"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp300238w"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm3010885"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.103"},{"key":"e_1_2_9_15_1","first-page":"77","article-title":"Isolation of mononuclear cells and granulocytes from human blood. 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