{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:06:38Z","timestamp":1791846398045,"version":"4.3.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"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":[[2011,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The C5a anaphylatoxin receptor (C5aR; CD88) is activated as part of the complement cascade and exerts important inflammatory, antimicrobial, and regulatory functions, at least in part, via crosstalk with TLRs. However, the periodontal pathogen Porphyromonas gingivalis can control C5aR activation by generating C5a through its own C5 convertase-like enzymatic activity. In this paper, we show that P. gingivalis uses this mechanism to proactively and selectively inhibit TLR2-induced IL-12p70, whereas the same pathogen-instigated C5aR-TLR2 crosstalk upregulates other inflammatory and bone-resorptive cytokines (IL-1\u03b2, IL-6, and TNF-\u03b1). In vivo, the ability of P. gingivalis to manipulate TLR2 activation via the C5a-C5aR axis allowed it to escape IL-12p70\u2013dependent immune clearance and to cause inflammatory bone loss in a murine model of experimental periodontitis. In the latter regard, C5aR-deficient or TLR2-deficient mice were both resistant to periodontal bone loss, in stark contrast with wild-type control mice, which is consistent with the interdependent interactions of C5aR and TLR2 in P. gingivalis immune evasion and induction of bone-resorptive cytokines. In conclusion, P. gingivalis targets C5aR to promote its adaptive fitness and cause periodontal disease. Given the current availability of safe and effective C5aR antagonists, pharmacological blockade of C5aR could act therapeutically in human periodontitis and reduce associated systemic risks.<\/jats:p>","DOI":"10.4049\/jimmunol.1003252","type":"journal-article","created":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T04:43:39Z","timestamp":1292301819000},"page":"869-877","source":"Crossref","is-referenced-by-count":165,"title":["The C5a Receptor Impairs IL-12\u2013Dependent Clearance of <i>Porphyromonas gingivalis<\/i> and Is Required for Induction of Periodontal Bone Loss"],"prefix":"10.1093","volume":"186","author":[{"given":"Shuang","family":"Liang","sequence":"first","affiliation":[{"name":"Center for Oral Health and Systemic Disease, University of Louisville Health Sciences Center , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Krauss","sequence":"additional","affiliation":[{"name":"Center for Oral Health and Systemic Disease, University of Louisville Health Sciences Center , Louisville, KY 40292"},{"name":"Department of Microbiology and Immunology, University of Louisville Health Sciences Center , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisanori","family":"Domon","sequence":"additional","affiliation":[{"name":"Center for Oral Health and Systemic Disease, University of Louisville Health Sciences Center , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan L","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Center for Oral Health and Systemic Disease, University of Louisville Health Sciences Center , Louisville, KY 40292"},{"name":"Department of Microbiology and Immunology, University of Louisville Health Sciences Center , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita B","family":"Hosur","sequence":"additional","affiliation":[{"name":"Center for Oral Health and Systemic Disease, University of Louisville Health Sciences Center , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchang","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenge","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Oral Health and Systemic Disease, University of Louisville Health Sciences Center , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolia","family":"Tzekou","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Lambris","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Hajishengallis","sequence":"additional","affiliation":[{"name":"Center for Oral Health and Systemic Disease, University of Louisville Health Sciences Center , Louisville, KY 40292"},{"name":"Department of Microbiology and Immunology, University of Louisville Health Sciences Center , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,1,15]]},"reference":[{"key":"2025032411012166900_r1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat. 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