{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:12:35Z","timestamp":1790802755275,"version":"4.1.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"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":[[2009,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Porphyromonas gingivalis, a Gram-negative bacterium that causes periodontitis, activates the kinin system via the cysteine protease R-gingipain. Using a model of buccal infection based on P. gingivalis inoculation in the anterior mandibular vestibule, we studied whether kinins released by gingipain may link mucosal inflammation to T cell-dependent immunity through the activation of bradykinin B2 receptors (B2R). Our data show that P. gingivalis W83 (wild type), but not gingipain-deficient mutant or wild-type bacteria pretreated with gingipain inhibitors, elicited buccal edema and gingivitis in BALB\/c or C57BL\/6 mice. Studies in TLR2\u2212\/\u2212, B2R\u2212\/\u2212, and neutrophil-depleted C57BL\/6 mice revealed that P. gingivalis induced edema through the sequential activation of TLR2\/neutrophils, with the initial plasma leakage being amplified by gingipain-dependent release of vasoactive kinins from plasma-borne kininogens. We then used fimbriae (Fim) Ag as a readout to verify whether activation of the TLR2\u2192PMN\u2192B2R axis (where PMN is polymorphonuclear neutrophil) at early stages of mucosal infection had impact on adaptive immunity. Analyzes of T cell recall responses indicated that gingipain drives B2R-dependent generation of IFN-\u03b3-producing Fim T cells in submandibular draining lymph nodes of BALB\/c and C57BL\/6 mice, whereas IL-17-producing Fim T cells were generated only in BALB\/c mice. In summary, our studies suggest that two virulence factors, LPS (an atypical TLR2 ligand) and gingipain, forge a trans-cellular cross-talk between TLR2 and B2R, thus forming an innate axis that guides the development of Fim-specific T cells in mice challenged intrabuccally by P. gingivalis. Ongoing research may clarify whether kinin-driven modulation of T cell responses may also influence the severity of chronic periodontitis.<\/jats:p>","DOI":"10.4049\/jimmunol.0900895","type":"journal-article","created":{"date-parts":[[2009,8,17]],"date-time":"2009-08-17T20:41:40Z","timestamp":1250541700000},"page":"3700-3711","source":"Crossref","is-referenced-by-count":57,"title":["Kinin Danger Signals Proteolytically Released by Gingipain Induce Fimbriae-Specific IFN-\u03b3- and IL-17-Producing T Cells in Mice Infected Intramucosally with\n                    <i>Porphyromonas gingivalis<\/i>"],"prefix":"10.1093","volume":"183","author":[{"given":"Ana Carolina","family":"Monteiro","sequence":"first","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Scovino","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susane","family":"Raposo","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics"},{"name":"Faculty of Odontology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Mussa","family":"Gaze","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics"},{"name":"Faculty of Odontology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia","family":"Cruz","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Svensj\u00f6","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Sampaio","family":"Narciso","sequence":"additional","affiliation":[{"name":"Department of Histology, Institute of Biomedical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Colombo","sequence":"additional","affiliation":[{"name":"Pablo de G\u00f3es Institute of Microbiology, Federal University of Rio de Janeiro , Rio de Janeiro,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o B","family":"Pesquero","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Federal University of S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Feres-Filho","sequence":"additional","affiliation":[{"name":"Faculty of Odontology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ky-Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Institute of Dental Research, Westmead Millenium Institute"},{"name":"Faculty of Dentistry, University of Sydney , Sydney,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Sroka","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry, Biophysics, and Biotechnology, Department of Microbiology, Jagiellonian University , Krakow,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry, Biophysics, and Biotechnology, Department of Microbiology, Jagiellonian University , Krakow,","place":["Poland"]},{"name":"Department of Periodontics, University of Louisville School of Dentistry , Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Scharfstein","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,9,15]]},"reference":[{"key":"2026012811250525200_R1"},{"key":"2026012811250525200_R2","first-page":"987","article-title":"B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease.","volume-title":"Am. 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Immunol.","year":"2007"},{"key":"2026012811250525200_R10","first-page":"37","article-title":"Interleukin-11 and IL-17 and the pathogenesis of periodontal disease.","volume-title":"J. Periodontol.","year":"2004"},{"key":"2026012811250525200_R11","first-page":"383","article-title":"Levels of interleukin-17 in gingival crevicular fluid and in supernatants of cellular cultures of gingival tissue from patients with chronic periodontitis.","volume-title":"J. Clin. Periodontol.","year":"2005"},{"key":"2026012811250525200_R12","first-page":"1545","article-title":"Gingival concentrations of interleukin-23 and -17 at healthy sites and at sites of clinical attachment loss.","volume-title":"J. 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Immun.","year":"1995"},{"key":"2026012811250525200_R24","first-page":"18896","article-title":"Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis.","volume-title":"J. Biol. Chem.","year":"1992"},{"key":"2026012811250525200_R25","first-page":"406","article-title":"Lysine- and arginine-specific proteinases from Porphyromonas gingivalis: isolation, characterization, and evidence for the existence of complexes with hemagglutinins.","volume-title":"J. Biol. Chem.","year":"1994"},{"key":"2026012811250525200_R26","first-page":"7935","article-title":"Purification and characterization of a potent 70-kDa thiol lysyl- proteinase (Lys-gingivain) from Porphyromonas gingivalis that cleaves kininogens and fibrinogen.","volume-title":"J. Biol. 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Microbiol.","year":"2008"},{"key":"2026012811250525200_R38","first-page":"361","article-title":"Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein\/kinin pathway.","volume-title":"J. Clin. Invest.","year":"1994"},{"key":"2026012811250525200_R39","first-page":"1999","article-title":"Dependence of vascular permeability enhancement on cysteine proteinases in vesicles of Porphyromonas gingivalis.","volume-title":"Infect. Immun.","year":"1995"},{"key":"2026012811250525200_R40","first-page":"1","article-title":"Bioregulation of kinins: kallikreins, kininogens, and kininases.","volume-title":"Pharmacol. Rev.","year":"1992"},{"key":"2026012811250525200_R41","first-page":"385","article-title":"Kinin receptors.","volume-title":"Clin. Rev. Allergy Immunol.","year":"1998"},{"key":"2026012811250525200_R42","first-page":"27","article-title":"International Union of Pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences.","volume-title":"Pharmacol. Rev.","year":"2005"},{"key":"2026012811250525200_R43","first-page":"5349","article-title":"Cutting Edge: bradykinin induces IL-12 production by dendritic cells: a danger signal that drives Th1 polarization.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811250525200_R44","first-page":"521","article-title":"Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies.","volume-title":"Peptides","year":"2004"},{"key":"2026012811250525200_R45","first-page":"18","article-title":"Activation of TAFI on the surface of Streptococcus pyogenes evokes inflammatory reactions by modulating the kallikrein\/kinin system.","volume-title":"J. Innate Immun.","year":"2009"},{"key":"2026012811250525200_R46","first-page":"6325","article-title":"Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type 1 immunity in a mouse model of subcutaneous infection by Trypanosoma cruzi.","volume-title":"J. 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