{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:13:47Z","timestamp":1790345627048,"version":"4.1.0"},"reference-count":288,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T00:00:00Z","timestamp":1522886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIDCR","award":["DE023567"],"award-info":[{"award-number":["DE023567"]}]},{"name":"NIH\/NIDCR","award":["DE024275"],"award-info":[{"award-number":["DE024275"]}]},{"name":"NIH\/NIDDK","award":["DK101711"],"award-info":[{"award-number":["DK101711"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following the sensing of danger-associated molecular patterns (DAMPs) generated as a consequence of cellular injury. Due to their essential role as DAMP and PAMP sensors, TLR signaling also contributes importantly to several systemic diseases including cardiovascular disease, diabetes, and others. The overlapping participation of TLRs in the control of infection, and pathogenesis of systemic diseases, has served as a starting point for research delving into the poorly defined area of infection leading to increased risk of various systemic diseases. Although conflicting studies exist, cardiovascular disease, diabetes, cancer, rheumatoid arthritis, and obesity\/metabolic dysfunction have been associated with differing degrees of strength to infectious diseases. Here we will discuss elements of these connections focusing on the contributions of TLR signaling as a consequence of bacterial exposure in the context of the oral infections leading to periodontal disease, and associations with metabolic diseases including atherosclerosis and type 2 diabetes.<\/jats:p>","DOI":"10.3390\/vaccines6020021","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T16:50:58Z","timestamp":1522947058000},"page":"21","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Linkage of Infection to Adverse Systemic Complications: Periodontal Disease, Toll-Like Receptors, and Other Pattern Recognition Systems"],"prefix":"10.3390","volume":"6","author":[{"given":"Shannon","family":"Wallet","sequence":"first","affiliation":[{"name":"Department of Oral Biology, College of Dental Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwajeet","family":"Puri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Diabetes Institute, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dental Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0092-8674(00)80172-5","article-title":"The dorsoventral regulatory gene cassette spatzle\/toll\/cactus controls the potent antifungal response in drosophila adults","volume":"86","author":"Lemaitre","year":"1996","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/41131","article-title":"A human homologue of the drosophila toll protein signals activation of adaptive immunity","volume":"388","author":"Medzhitov","year":"1997","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","article-title":"Defective LPS Signaling in C3H\/HeJ and C57BL\/10ScCr Mice: Mutations in Tlr4 Gene","volume":"282","author":"Poltorak","year":"1998","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bbrc.2009.08.062","article-title":"Toll-like receptors and innate immunity","volume":"388","author":"Kumar","year":"2009","journal-title":"Biochem. 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