{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:14:50Z","timestamp":1785352490228,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Background: Oral pathogens may exert the ability to trigger differently the activation of local macrophage immune responses, for instance Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans induce predominantly pro-inflammatory (M1-like phenotypes) responses, while oral commensal microbiota primarily elicits macrophage functions consistent with the anti-inflammatory (M2-like phenotypes). Methods: In healthy individuals vs. periodontal disease patients\u2019 blood samples, the differentiation process from monocyte to M1 and M2 was conducted using two typical growth factors, the granulocyte\/macrophage colony stimulating factor (GM-CSF) and the macrophage colony stimulating factor (M-CSF). Results: In contrast with the current literature our outcomes showed a noticeable increase of macrophage polarization from healthy individuals vs. periodontal patients. The biological and clinical significance of these data was discussed. Conclusions: Our translational findings showed a significant variance between control versus periodontal disease groups in M1 and M2 marker expression within the second group significantly lower skews differentiation of M2-like macrophages towards an M1-like phenotype. Macrophage polarization in periodontal tissue may be responsible for the development and progression of inflammation-induced periodontal tissue damage, including alveolar bone loss, and modulating macrophage function may be a potential strategy for periodontal disease management.<\/jats:p>","DOI":"10.3390\/biology9060131","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T13:20:43Z","timestamp":1592313643000},"page":"131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Oral Microbiota and Immune System Crosstalk: A Translational Research"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-1415","authenticated-orcid":false,"given":"Andrea","family":"Ballini","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari \u201cAldo Moro\u201d, Campus Universitario \u201cErnesto Quagliariello\u201d, 70125 Bari, Italy"},{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"},{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Dipalma","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro Gargiulo","family":"Isacco","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"},{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"Boccellino","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Di Domenico","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-8124","authenticated-orcid":false,"given":"Luigi","family":"Santacroce","sequence":"additional","affiliation":[{"name":"Ionian Department, Microbiology and Virology Laboratory, Policlinico University Hospital, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieu C.D.","family":"Nguy\u1ec5n","sequence":"additional","affiliation":[{"name":"Human Stem Cell\u2019s HSC, Ho Chi Minh City 70000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-2489","authenticated-orcid":false,"given":"Salvatore","family":"Scacco","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-4706","authenticated-orcid":false,"given":"Maura","family":"Calvani","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Boddi","sequence":"additional","affiliation":[{"name":"Biomolecular Diagnostic Srl, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Corcioli","sequence":"additional","affiliation":[{"name":"Biomolecular Diagnostic Srl, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Quagliuolo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-2521","authenticated-orcid":false,"given":"Stefania","family":"Cantore","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Saverio","family":"Martelli","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"},{"name":"Biomolecular Diagnostic Srl, 50139 Florence, Italy"},{"name":"IMI (International Microdentistry Institute), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Inchingolo","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"674","DOI":"10.7150\/ijms.6962","article-title":"Cytokine gene polymorphisms associate with microbiogical agents in periodontal disease: Our experience","volume":"11","author":"Cantore","year":"2014","journal-title":"Int. J. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2174\/1871530319666181221150352","article-title":"Probiotics efficacy on oxidative stress values in inflammatory bowel disease: A randomized double-blinded placebo-controlled pilot study","volume":"19","author":"Ballini","year":"2019","journal-title":"Endocr. Metab. Immune. Disord. Drug Targets"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Inchingolo, F., Martelli, F.S., Gargiulo Isacco, C., Borsani, E., Cantore, S., Corcioli, F., Boddi, A., Nguy\u1ec5n, K.C.D., De Vito, D., and Aityan, S.K. (2020). Chronic Periodontitis and Immunity, Towards the Implementation of a Personalized Medicine: A Translational Research on Gene Single Nucleotide Polymorphisms (SNPs) Linked to Chronic Oral Dysbiosis in 96 Caucasian Patients. Biomedicines, 8.","DOI":"10.3390\/biomedicines8050115"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1177\/039463200902200111","article-title":"Osteoblast apoptosis in periodontal disease: Role of TNF-related apoptosis-inducing ligand","volume":"22","author":"Mori","year":"2009","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_5","first-page":"S1","article-title":"A new classification scheme for periodontal and peri-implant diseases and conditions-Introduction and key changes from the 1999 classification","volume":"89","author":"Caton","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The Chemokine System in Diverse Forms of Macrophage Activation and Polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/jcp.24301","article-title":"Human monocyte-derived macrophages spontaneously differentiated in vitro show distinct phenotypes","volume":"228","author":"Eligini","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_8","first-page":"273","article-title":"Periodontal disease and bone pathogenesis: The crosstalk between cytokines and porphyromonas gingivalis","volume":"29","author":"Ballini","year":"2015","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_9","first-page":"1323","article-title":"Microbiological results of improvement in periodontal condition by administration of oral Probiotics","volume":"32","author":"Inchingolo","year":"2018","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1128\/IAI.73.2.935-943.2005","article-title":"Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its lipopolysaccharide, or its FimA protein","volume":"73","author":"Zhou","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s00404-011-2138-9","article-title":"Microbiological findings in endometrial specimen: Our experience","volume":"285","author":"Cicinelli","year":"2012","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1182\/blood-2005-10-4144","article-title":"IL-10 producing macrophages preferentially clear apoptotic cells","volume":"107","author":"Xu","year":"2006","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.cyto.2012.08.008","article-title":"Cloning and expression of porcine Colony Stimulating Factor-1 (CSF-1) and Colony Stimulating Factor-1 Receptor (CSF-1R) and analysis of the species specificity of stimulation by CSF-1 and Interleukin 34","volume":"60","author":"Gow","year":"2012","journal-title":"Cytokine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.2353\/ajpath.2008.070513","article-title":"Heterogeneity of human macrophages in culture and in atherosclerotic plaques","volume":"172","author":"Waldo","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 paradigm of macrophage activation: Time for reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000 Prime Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3292810","DOI":"10.1155\/2017\/3292810","article-title":"Mesenchymal stem cells as promoters, enhancers, and playmakers of the translational regenerative medicine","volume":"2017","author":"Ballini","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.archoralbio.2017.03.006","article-title":"Enhanced activity of macrophage M1\/M2 phenotypes in periodontitis","volume":"96","author":"Yang","year":"2018","journal-title":"Arch. Oral. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8468","DOI":"10.1074\/jbc.M111.290676","article-title":"Classically activated macrophages use stable microtubules for matrix metalloproteinase-9 (MMP-9) secretion","volume":"287","author":"Hanania","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ricci, S., Pinto, F., Auletta, A., Giordano, A., Giovane, A., Settembre, G., Boccellino, M., Boffo, S., Di Carlo, A., and Di Domenico, M. (2019). The enigmatic role of matrix metalloproteinases in epithelial-to-mesenchymal transition of oral squamous cell carcinoma: Implications and nutraceutical aspects. J. Cell. Biochem., 3.","DOI":"10.1002\/jcb.26905"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage activation and polarization: Nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"ref_21","first-page":"1087","article-title":"Intraoral lymphoepithelial carcinoma of the minor salivary glands","volume":"26","author":"Menditti","year":"2012","journal-title":"In Vivo"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.18632\/oncotarget.21327","article-title":"Aggressiveness pattern and second primary tumor risk associated with basaloid squamous cell carcinoma of the larynx","volume":"8","author":"Ricciardiello","year":"2017","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1002\/jbmr.2735","article-title":"Macrophages: Their Emerging Roles in Bone","volume":"30","author":"Sinder","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/ni.2705","article-title":"Tissue-resident macrophages","volume":"14","author":"Davies","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642","DOI":"10.7150\/ijms.4998","article-title":"Effect of different irrigating solutions and endodontic sealers on bond strength of the dentin-post interface with and without defects","volume":"9","author":"Grassi","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_26","first-page":"863","article-title":"Cytokine genotype distribution in patients with periodontal disease and rheumatoid arthritis or diabetes mellitus","volume":"30","author":"Crincoli","year":"2016","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1189\/jlb.0909624","article-title":"Pivotal advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products","volume":"87","author":"Garceau","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00011-015-0874-1","article-title":"Macrophage polarization: The link between inflammation and related diseases","volume":"65","author":"Bashir","year":"2016","journal-title":"Inflamm. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.3889\/oamjms.2018.406","article-title":"Probiotics Improve Urogenital Health in Women","volume":"6","author":"Ballini","year":"2018","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1161\/hc0702.104178","article-title":"Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model","volume":"105","author":"Li","year":"2002","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1902\/jop.2001.72.10.1398","article-title":"Is collagen breakdown during periodontitis linked to inflammatory cells and expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival tissue?","volume":"72","author":"Seguier","year":"2001","journal-title":"J. Periodontol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1600-0765.1989.tb00864.x","article-title":"Phenotypic dynamics of macrophage subpopulations during human experimental gingivitis","volume":"24","author":"Topoll","year":"1989","journal-title":"J. Periodontal Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s40496-014-0017-8","article-title":"Immuno-pathogenesis of Periodontal Disease: Current and Emerging Paradigms","volume":"1","author":"Huang","year":"2014","journal-title":"Curr. Oral Health Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"395","DOI":"10.4103\/1735-3327.218563","article-title":"Association of macrophage migration inhibitory factor gene polymorphisms with chronic periodontitis in a South Eastern Iranian population","volume":"14","author":"Heidari","year":"2017","journal-title":"Dent. Res. J."},{"key":"ref_35","first-page":"1","article-title":"Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions","volume":"8","author":"Letta","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3389\/fimmu.2017.00691","article-title":"Brucella Dysregulates Monocytes and Inhibits Macrophage Polarization through LC3-Dependent Autophagy","volume":"8","author":"Wang","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e01820-16","DOI":"10.1128\/mBio.01820-16","article-title":"Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions","volume":"8","author":"Wagener","year":"2017","journal-title":"mBio"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3389\/fnagi.2017.00327","article-title":"Periodontitis and Alzheimer\u2019s Disease: A Possible Comorbidity between Oral Chronic Inflammatory Condition and Neuroinflammation","volume":"9","author":"Teixeira","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/S0002-9440(10)62367-X","article-title":"Platelet-activating factor regulates cadherin-catenin adhesion system expression and beta-catenin phosphorylation during Kaposi\u2019s sarcoma cell motility","volume":"166","author":"Boccellino","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1111\/jcpe.13156","article-title":"Characterization of macrophage polarization in periodontal disease","volume":"46","author":"Fretwurst","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/(SICI)1096-9896(1998110)186:3<281::AID-PATH200>3.0.CO;2-7","article-title":"Failure of macrophage activation in destructive periodontal disease","volume":"186","author":"Chapple","year":"1998","journal-title":"J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s00204-005-0046-0","article-title":"Lack of genotoxic effect in workers exposed to very low doses of 1,3-butadiene","volume":"80","author":"Lovreglio","year":"2006","journal-title":"Arch. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1002\/jcb.24000","article-title":"In vitro model of stromal and epithelial immortalized endometriotic cells","volume":"113","author":"Boccellino","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1177\/039463201002300234","article-title":"The role of anti-cyclic citrullinated peptide antibody in periodontal disease","volume":"23","author":"Ballini","year":"2010","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_45","first-page":"433","article-title":"IL-1 haplotype analysis in periodontal disease","volume":"32","author":"Ballini","year":"2018","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_46","first-page":"1173","article-title":"Anti-plaque and antimicrobial efficiency of different oral rinses in a 3-day plaque accumulation model","volume":"30","author":"Cantore","year":"2016","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_47","first-page":"115","article-title":"Isobornyl acrylate: An impurity in alkyl glucosides","volume":"35","author":"Foti","year":"2016","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Magrone, T., Magrone, M., Russo, M.A., and Jirillo, E. (2020). Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison. A Dietary Approach. Endocr. Metab. Immune. Disord. Drug Targets.","DOI":"10.2174\/1871530320666200406123734"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/9\/6\/131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:39:38Z","timestamp":1760175578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/9\/6\/131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,16]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["biology9060131"],"URL":"https:\/\/doi.org\/10.3390\/biology9060131","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,16]]}}}