{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:19:35Z","timestamp":1793827175711,"version":"4.6.1"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The mechanisms that underlie valvular inflammation in streptococcus-induced infective endocarditis (IE) remain unclear. We previously demonstrated that streptococcal glucosyltransferases (GTFs) can activate human heart valvular interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that activated VIC can enhance neutrophil infiltration through sustained IL-17 production, leading to valvular damage. To monitor cytokine and chemokine production, leukocyte recruitment, and the induction or expansion of CD4<jats:sup>+<\/jats:sup>CD45RA<jats:sup>\u2212<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>CCR6<jats:sup>+<\/jats:sup>Th17 cells, primary human VIC were cultured<jats:italic>in vitro<\/jats:italic>and activated by GTFs. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by immunohistochemistry in infected valves from patients with IE. The expression of IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (<jats:italic>Rorc<\/jats:italic>) was upregulated in GTF-activated VIC, which may enhance the proliferation of memory Th17 cells in an IL-6-dependent manner. Many chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC, which might recruit neutrophils and CD4<jats:sup>+<\/jats:sup>T cells. Moreover, CXCL1 production in VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were increased in patients with IE compared to healthy donors. Furthermore, elevated serum IL-21 levels have been significantly associated with severe valvular damage, including rupture of chordae tendineae, in IE patients. Our findings suggest that VIC are activated by bacterial modulins to recruit neutrophils and that such activities might be further enhanced by the production of Th17-associated cytokines. Together, these factors can amplify the release of neutrophilic contents<jats:italic>in situ<\/jats:italic>, which might lead to severe valvular damage.<\/jats:p>","DOI":"10.1128\/iai.02965-14","type":"journal-article","created":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T02:12:30Z","timestamp":1426558350000},"page":"2202-2212","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Activated Human Valvular Interstitial Cells Sustain Interleukin-17 Production To Recruit Neutrophils in Infective Endocarditis"],"prefix":"10.1128","volume":"83","author":[{"given":"Chiou-Yueh","family":"Yeh","sequence":"first","affiliation":[{"name":"Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Tung","family":"Shun","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Min","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiau-Jing","family":"Jung","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Chou","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Ling","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Far Eastern Memorial Hospital, Taipei, Taiwan, Republic of China"},{"name":"Graduate Program of Biomedical Informatics, Yuan Ze University, Chung-Li, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeng-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron-Bin","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ju","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-San","family":"Chia","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra010082"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06903.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0011-8532(22)01165-X","article-title":"Controversies in the prevention of infective endocarditis related to dental procedures","volume":"34","author":"Fekete T","year":"1990","unstructured":"Fekete T. 1990. 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