title: Induction of cytokines by glucosyltransferases of streptococcus mutans.
abstract: Production of proinflammatory cytokines is implicated in the pathogenesis of viridans streptococcus-induced alpha-streptococcal shock syndrome and infective endocarditis. Streptococcus mutans, one of the opportunistic pathogens causing infective endocarditis, was reported previously to stimulate monocytes and epithelial and endothelial cells in vitro to produce various cytokines. We found that glucosyltransferases (GTFs) GtfC and GtfD of S. mutans stimulated predominantly the production of interleukin-6 (IL-6) from T cells cultured in vitro. The level of IL-6 but not of tumor necrosis factor alpha in blood was significantly elevated when rats were injected intravenously with S. mutans GS-5, whereas IL-6 was detected at a much lower level when rats were challenged with NHS1DD, an isogenic mutant defective in the expression of GTFs. The serum IL-6 level was elevated in patients with endocarditis caused by different species of viridans streptococci which express GTF homologues. Affinity column-purified GTFs reduced the levels of detectable IL-2 of T cells stimulated by another bacterial antigen, tetanus toxoid. These results suggested that GTFs might modulate the production of Th1-type cytokines and that GTFs of S. mutans play a significant role in stimulating the production of the proinflammatory cytokine IL-6 in vivo.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China. chiajs@ha.mc.ntu.edu.tw
authors.forename: Jean-San
authors.initials: JS
authors.lastname: Chia
authors.forename: Huei-Ting
authors.initials: HT
authors.lastname: Lien
authors.forename: Po-Ren
authors.initials: PR
authors.lastname: Hsueh
authors.forename: Pei-Min
authors.initials: PM
authors.lastname: Chen
authors.forename: Andy
authors.initials: A
authors.lastname: Sun
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002648:Child; D016207:Cytokines / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005964:Glucosyltransferases / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013295:Streptococcus mutans / Q000201:enzymology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D015850:Interleukin-6; D005964:Glucosyltransferases; C110463:glucosyltransferase C; C113848:glucosyltransferase D