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Prevention of vertical transmission is not possible because of lack of an approved therapy for use in pregnancy or an effective vaccine. Recently, HCV has been identified as an independent risk factor for preterm delivery, perinatal mortality, and other complications. In this study, we characterized the immune responses that contribute to the control of viral infection at the maternal\u2013fetal interface (MFI) in the early gestational stages. In this study, we show that primary human trophoblast cells and an extravillous trophoblast cell line (HTR8), from first and second trimester of pregnancy, express receptors relevant for HCV binding\/entry and are permissive for HCV uptake. We found that HCV\u2013RNA sensing by human trophoblast cells induces robust upregulation of type I\/III IFNs and secretion of multiple chemokines that elicit recruitment and activation of decidual NK cells. Furthermore, we observed that HCV\u2013RNA transfection induces a proapoptotic response within HTR8 that could affect the morphology of the placenta. To our knowledge, for the first time, we demonstrate that HCV\u2013RNA sensing by human trophoblast cells elicits a strong antiviral response that alters the recruitment and activation of innate immune cells at the MFI. This work provides a paradigm shift in our understanding of HCV-specific immunity at the MFI as well as novel insights into mechanisms that limit vertical transmission but may paradoxically lead to virus-related pregnancy complications.<\/jats:p>","DOI":"10.4049\/jimmunol.1500409","type":"journal-article","created":{"date-parts":[[2015,9,4]],"date-time":"2015-09-04T22:28:47Z","timestamp":1441405727000},"page":"3737-3747","source":"Crossref","is-referenced-by-count":36,"title":["Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission"],"prefix":"10.1093","volume":"195","author":[{"given":"Silvia","family":"Giugliano","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret G","family":"Petroff","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryce D","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susmita","family":"Jasti","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Linscheid","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgenia","family":"Dobrinskikh","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A","family":"Sheiko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Michael","family":"Gale","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington, School of Medicine , Seattle, WA 98109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Golden-Mason","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia D","family":"Winn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Stanford University , Palo Alto, CA 94304"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo R","family":"Rosen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver , Aurora, CO 80045"},{"name":"Eastern Colorado Veteran\u2019s Affairs Medical Center , Denver, CO 80220"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"2025030704183128300_r1","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1056\/NEJMcp1006613","article-title":"Clinical practice: chronic hepatitis C infection","volume":"364","author":"Rosen","year":"2011","journal-title":"N. 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