{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:53:15Z","timestamp":1783133595726,"version":"3.54.6"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"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":[[2017,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Monocytes and macrophages (M\u03a6s) play a central role in the pathogenesis of chronic hepatitis C virus (HCV) infection. The tissue microenvironment triggers monocyte differentiation into M\u03a6s, with polarization ranging within the spectrum of M1 (classical) to M2 (alternative) activation. Recently, we demonstrated that HCV infection leads to monocyte differentiation into polarized M\u03a6s that mediate stellate cell activation via TGF-\u03b2. In this study, we aimed to identify the viral factor(s) that mediate monocyte-to-M\u03a6 differentiation. We performed coculture experiments using healthy monocytes with exosome-packaged HCV, cell-free HCV, or HCV ssRNA. Coculture of monocytes with exosome-packaged HCV, cell-free HCV, or HCV ssRNA induced differentiation into M\u03a6s with high M2 surface marker expression and production of pro- and anti-inflammatory cytokines. The HCV ssRNA\u2013induced monocyte activation and differentiation into M\u03a6s could be prevented by TLR7 or TLR8 knockdown. Furthermore, TLR7 or TLR8 stimulation, independent of HCV, caused monocyte differentiation and M2 M\u03a6 polarization. In vivo, in chronic HCV\u2013infected patients, we found increased expression of TLR7\/8 in circulating monocytes that was associated with increased intracellular expression of procollagen. Furthermore, knockdown of TLR8 completely attenuated collagen expression in monocytes exposed to HCV, and knockdown of TLR7 partially attenuated this expression, suggesting roles for TLR7\/8 in induction of fibrocytes in HCV infection. We identified TLR7\/8 as mediators of monocyte differentiation and M2 M\u03a6 polarization during HCV infection. Further, we demonstrated that HCV ssRNA and other TLR7\/8 ligands promote M\u03a6 polarization and generation of circulating fibrocytes.<\/jats:p>","DOI":"10.4049\/jimmunol.1600797","type":"journal-article","created":{"date-parts":[[2017,1,26]],"date-time":"2017-01-26T02:25:38Z","timestamp":1485397538000},"page":"1974-1984","source":"Crossref","is-referenced-by-count":48,"title":["Circulating and Exosome-Packaged Hepatitis C Single-Stranded RNA Induce Monocyte Differentiation via TLR7\/8 to Polarized Macrophages and Fibrocytes"],"prefix":"10.1093","volume":"198","author":[{"given":"Banishree","family":"Saha","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kodys","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5144-4064","authenticated-orcid":false,"given":"Adeyinka","family":"Adejumo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-2527","authenticated-orcid":false,"given":"Gyongyi","family":"Szabo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,3,1]]},"reference":[{"key":"2025031312193410800_r1","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/hep.26141","article-title":"Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence","volume":"57","author":"Mohd Hanafiah","year":"2013","journal-title":"Hepatology"},{"key":"2025031312193410800_r2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/hep.27259","article-title":"Global distribution and prevalence of hepatitis C virus genotypes","volume":"61","author":"Messina","year":"2015","journal-title":"Hepatology"},{"key":"2025031312193410800_r3","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/S0140-6736(14)62401-6","article-title":"Hepatitis C","volume":"385","author":"Webster","year":"2015","journal-title":"Lancet"},{"key":"2025031312193410800_r4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/cid\/civ220","article-title":"The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus","volume":"61","author":"Rein","year":"2015","journal-title":"Clin. 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