{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:32:25Z","timestamp":1792452745175,"version":"4.5.0"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2024,3,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically,\n                      <jats:italic>Streptococcus anginosus<\/jats:italic>\n                      is associated with esophageal, gastric, and pharyngeal cancers, while\n                      <jats:italic>Streptococcus mitis<\/jats:italic>\n                      is linked to oral cancer. However, no study has investigated the mechanistic links between these\n                      <jats:italic>Streptococcus<\/jats:italic>\n                      species and cancer-related inflammatory responses. As an initial step, we probed the innate immune response triggered by\n                      <jats:italic>S. anginosus<\/jats:italic>\n                      and\n                      <jats:italic>S. mitis<\/jats:italic>\n                      in RAW264.7 macrophages. These bacteria exerted time- and dose-dependent effects on macrophage morphology without affecting cell viability. Compared with untreated macrophages, macrophages infected with\n                      <jats:italic>S. anginosus<\/jats:italic>\n                      exhibited a robust proinflammatory response characterized by significantly increased levels of inflammatory cytokines and mediators, including TNF, IL-6, IL-1\u03b2, NOS2, and COX2, accompanied by enhanced NF-\u03baB activation. In contrast,\n                      <jats:italic>S. mitis<\/jats:italic>\n                      -infected macrophages failed to elicit a robust inflammatory response. Seahorse Xfe96 analysis revealed an increased extracellular acidification rate in macrophages infected with\n                      <jats:italic>S. anginosus<\/jats:italic>\n                      compared with\n                      <jats:italic>S. mitis<\/jats:italic>\n                      . At the 24-h time point, the presence of\n                      <jats:italic>S. anginosus<\/jats:italic>\n                      led to reduced extracellular itaconate, while\n                      <jats:italic>S. mitis<\/jats:italic>\n                      triggered increased itaconate levels, highlighting distinct metabolic profiles in macrophages during infection in contrast to aconitate decarboxylase expression observed at the 6-h time point. This initial investigation highlights how\n                      <jats:italic>S. anginosus<\/jats:italic>\n                      and\n                      <jats:italic>S. mitis<\/jats:italic>\n                      , two Gram-positive bacteria from the same genus, can prompt distinct immune responses and metabolic shifts in macrophages during infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The surge in head and neck cancer cases among individuals devoid of typical risk factors such as Human Papilloma Virus (HPV) infection and tobacco and alcohol use sparks an argumentative discussion around the emerging role of oral microbiota as a novel risk factor in oral squamous cell carcinoma (OSCC). While substantial research has dissected the gut microbiome\u2019s influence on physiology, the oral microbiome, notably oral streptococci, has been underappreciated during mucosal immunopathogenesis.\n                        <jats:italic>Streptococcus anginosus<\/jats:italic>\n                        , a viridans streptococci group, has been linked to abscess formation and an elevated presence in esophageal cancer and OSCC. The current study aims to probe the innate immune response to\n                        <jats:italic>S. anginosus<\/jats:italic>\n                        compared with the early colonizer\n                        <jats:italic>Streptococcus mitis<\/jats:italic>\n                        as an important first step toward understanding the impact of distinct oral\n                        <jats:italic>Streptococcus<\/jats:italic>\n                        species on the host immune response, which is an understudied determinant of OSCC development and progression.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00536-23","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T09:05:32Z","timestamp":1706605532000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Oral streptococci\n                    <i>S. anginosus<\/i>\n                    and\n                    <i>S. mitis<\/i>\n                    induce distinct morphological, inflammatory, and metabolic signatures in macrophages"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1004-0773","authenticated-orcid":false,"given":"Sangeetha","family":"Senthil Kumar","sequence":"first","affiliation":[{"name":"Department of Immunobiology, College of Medicine, The University of Arizona, Tucson, Arizona, USA"},{"name":"The University of Arizona Cancer Center, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venugopal","family":"Gunda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakota M.","family":"Reinartz","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, College of Medicine, The University of Arizona, Tucson, Arizona, USA"},{"name":"The University of Arizona Cancer Center, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin W.","family":"Pond","sequence":"additional","affiliation":[{"name":"The University of Arizona Cancer Center, Tucson, Arizona, USA"},{"name":"Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis A.","family":"Thorne","sequence":"additional","affiliation":[{"name":"The University of Arizona Cancer Center, Tucson, Arizona, USA"},{"name":"Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Victor","family":"Santiago Raj","sequence":"additional","affiliation":[{"name":"R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6347-0208","authenticated-orcid":true,"given":"Michael D. 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