{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:26:49Z","timestamp":1783524409388,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T00:00:00Z","timestamp":1468972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE020820"],"award-info":[{"award-number":["R01DE020820"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Oral Microbiology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"Summary<\/jats:title>Toll\u2010like\u2010receptors (TLR<\/jats:styled-content>s) play a significant role in the generation of a specific innate immune response against invading pathogens. TLR<\/jats:styled-content>2 and\u00a0TLR<\/jats:styled-content>4 signaling contributes to infection\u2010induced\u00a0inflammation in periodontal disease (PD<\/jats:styled-content>) and atherosclerosis. Observational studies point towards a relationship between PD<\/jats:styled-content> and atherosclerosis, but the role of TLR<\/jats:styled-content>2 and TLR<\/jats:styled-content>4 in the recognition of multiple oral pathogens and their modulation of host response leading to atherosclerosis are not clear. We evaluated the role of TLR<\/jats:styled-content>2 and TLR<\/jats:styled-content>4 signaling in the induction of both PD<\/jats:styled-content> and atherosclerosis in TLR<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup> and TLR<\/jats:styled-content>4\u2212\/\u2212<\/jats:sup> mice to polymicrobial infection with periodontal pathogens Porphyromonas gingivalis<\/jats:italic>, Treponema denticola<\/jats:italic>, Tannerella forsythia<\/jats:italic>, and Fusobacterium nucleatum<\/jats:italic>. Polybacterial infections have established gingival colonization in TLR<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup> and TLR<\/jats:styled-content>4\u2212\/\u2212<\/jats:sup> mice and induction of a pathogen\u2010specific immunoglobulin G immune response. But TLR<\/jats:styled-content> deficiency dampened accelerated alveolar bone resorption and intrabony defects, indicating a central role in infection\u2010induced PD<\/jats:styled-content>. Periodontal bacteria disseminated from gingival tissue to the heart and aorta through intravascular dissemination; however, there was no increase in atherosclerosis progression in the aortic arch. Polybacterial infection does not alter levels of serum risk factors such as oxidized low\u2010density lipoprotein, nitric oxide, and lipid fractions in both mice. Polymicrobial\u2010infected TLR<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup> mice demonstrated significant levels (P\u00a0<\/jats:italic><\u00a00.05 to P\u00a0<\/jats:italic><\u00a00.01) of T helper type 2 [transforming growth factor\u2010\u03b21<\/jats:sub>, macrophage inflammatory protein\u20103\u03b1, interleukin\u201013 (IL<\/jats:styled-content>\u201013)] and T helper type 17 (IL<\/jats:styled-content>\u201017, IL<\/jats:styled-content>\u201021, IL<\/jats:styled-content>\u201022, IL<\/jats:styled-content>\u201023) splenic T\u2010cell cytokine responses. Increased heat\u2010shock protein expression, hspa1a<\/jats:italic> for Hsp 70, was observed for both TLR<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup> and TLR<\/jats:styled-content>4\u2212\/\u2212<\/jats:sup> mice. This study supports a role for TLR<\/jats:styled-content>2 and TLR<\/jats:styled-content>4 in PD<\/jats:styled-content> and atherosclerosis, corroborating an intricate association between two inflammatory diseases.<\/jats:p>","DOI":"10.1111\/omi.12165","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T19:33:03Z","timestamp":1464204783000},"page":"211-225","source":"Crossref","is-referenced-by-count":39,"title":["Global TLR<\/scp>2 and 4 deficiency in mice impacts bone resorption, inflammatory markers and atherosclerosis to polymicrobial infection"],"prefix":"10.1111","volume":"32","author":[{"given":"S.S.","family":"Chukkapalli","sequence":"first","affiliation":[{"name":"Department of Periodontology College of Dentistry University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.M.","family":"Velsko","sequence":"additional","affiliation":[{"name":"Department of Periodontology College of Dentistry University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.F.","family":"Rivera\u2010Kweh","sequence":"additional","affiliation":[{"name":"Department of Periodontology College of Dentistry University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Larjava","sequence":"additional","affiliation":[{"name":"Division of Periodontics and Dental Hygiene University of British Columbia Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.R.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Department of Medicine University of Florida Gainesville FL USA"},{"name":"Molecular Genetics & Microbiology College of Medicine University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Kesavalu","sequence":"additional","affiliation":[{"name":"Department 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