{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:02:10Z","timestamp":1791820930215,"version":"4.3.4"},"reference-count":68,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: This review synthesizes the role of Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) in modulating immune responses through citrullination and assesses its impact on periodontitis and systemic conditions. Methods: A systematic review was conducted on preclinical and clinical studies focusing on P. gingivalis- and A. actinomycetemcomitans-induced citrullination and its effects on immune responses, particularly inflammatory pathways, and systemic diseases. The search included PubMed, Scopus, Google Scholar, Web of Science, and gray literature. Quality and risk of bias were assessed using OHAT Rob Toll and QUIN-Tool. The review is registered in PROSPERO (ID: CRD42024579352). Results: 18 articles published up to August 2024 were included. Findings show that P. gingivalis and A. actinomycetemcomitans citrullination modulates immune responses, leading to neutrophil dysfunction and chronic inflammation. Key mechanisms include citrullination of antimicrobial peptides, CXCL10, histone H3, \u03b1-enolase, and C5a, impairing neutrophil activation and promoting NET formation. Conclusions: This review suggests that P. gingivalis and A. actinomycetemcomitans citrullination modulates immune responses and may influence periodontitis and systemic conditions like RA. Beyond ACPA production, these pathogens affect key proteins such as H3, C5a, and CXCL10, as well as antimicrobial peptides, NET formation, and phagocytosis. These interactions lead to neutrophil dysfunction and potentially affect other cells, subsequently disrupting local and systemic inflammatory responses.<\/jats:p>","DOI":"10.3390\/jcm13226831","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T09:59:11Z","timestamp":1731491951000},"page":"6831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of Protein Citrullination by Periodontal Pathobionts on Oral and Systemic Health: A Systematic Review of Preclinical and Clinical Studies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9358-6948","authenticated-orcid":false,"given":"Marco","family":"Bonilla","sequence":"first","affiliation":[{"name":"Higher Technician in Clinical and Biomedical Laboratory, Centro de Investigaci\u00f3n Biom\u00e9dica (CIBM), 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3540-1085","authenticated-orcid":false,"given":"Natividad","family":"Mart\u00edn-Morales","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Granada, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria (IBS Institute), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"G\u00e1lvez-Rueda","sequence":"additional","affiliation":[{"name":"Independent Researcher, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Raya-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Granada, 18016 Granada, Spain"},{"name":"Department of Rheumatology, San Cecilio University Clinical Hospital, 18006 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-2527","authenticated-orcid":false,"given":"Francisco","family":"Mesa","sequence":"additional","affiliation":[{"name":"Department of Periodontics, School of Dentistry, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41577-020-00488-6","article-title":"Local and Systemic Mechanisms Linking Periodontal Disease and Inflammatory Comorbidities","volume":"21","author":"Hajishengallis","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2174\/157339511794474226","article-title":"Oral Pathogens, Immunity, and Periodontal Diseases","volume":"7","author":"Mesa","year":"2011","journal-title":"Curr. Immunol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s12010-022-04127-9","article-title":"Periodontitis: An Oral Disease with Severe Consequences","volume":"195","author":"Ray","year":"2022","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/jcpe.13769","article-title":"Prevalence of Periodontitis in Dentate People Between 2011 and 2020: A Systematic Review and Meta-Analysis of Epidemiological Studies","volume":"50","author":"Trindade","year":"2023","journal-title":"J. Clin. Periodontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/prd.12296","article-title":"The Role of the Microbiota in Periodontal Disease","volume":"83","author":"Curtis","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Horvat Aleksijevi\u0107, L., Aleksijevi\u0107, M., \u0160krlec, I., \u0160ram, M., and Talapko, J. (2022). Porphyromonas gingivalis Virulence Factors and Clinical Significance in Periodontal Disease and Coronary Artery Diseases. Pathogens, 11.","DOI":"10.3390\/pathogens11101173"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/bs.apcsb.2019.12.001","article-title":"Roles of Porphyromonas gingivalis and Its Virulence Factors in Periodontitis","volume":"120","author":"Xu","year":"2020","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Di Stefano, M., Polizzi, A., Santonocito, S., Romano, A., Lombardi, T., and Isola, G. (2022). Impact of Oral Microbiome in Periodontal Health and Periodontitis: A Critical Review on Prevention and Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095142"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/prd.12430","article-title":"Interconnection of Periodontal Disease and Comorbidities: Evidence, Mechanisms, and Implications","volume":"9","author":"Hajishengallis","year":"2022","journal-title":"Periodontology 2000"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/prd.12331","article-title":"Current Understanding of Periodontal Disease Pathogenesis and Targets for Host-Modulation Therapy","volume":"84","author":"Hajishengallis","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s12276-024-01219-w","article-title":"Neutrophils and Neutrophil Extracellular Traps in Oral Health and Disease","volume":"56","author":"Kim","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mag\u00e1n-Fern\u00e1ndez, A., Al-Bakri, S.M.R., O\u2019Valle, F., Benavides-Reyes, C., Abad\u00eda-Molina, F., and Mesa, F. (2020). Neutrophil Extracellular Traps in Periodontitis. Cells, 9.","DOI":"10.3390\/cells9061494"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bryzek, D., Ciaston, I., Dobosz, E., Gasiorek, A., Makarska, A., Sarna, M., Eick, S., Puklo, M., Lech, M., and Potempa, B. (2019). Triggering NETosis via Protease-Activated Receptor (PAR)-2 Signaling as a Mechanism of Hijacking Neutrophil Function for Pathogen Benefits. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007773"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, J., Tong, Y., Zhu, Q., Gao, L., and Sun, Y. (2022). Neutrophil Extracellular Traps Induced by Porphyromonas gingivalis Lipopolysaccharide Modulate Inflammatory Responses via a Ca2+-Dependent Pathway. Arch. Oral Biol., 141.","DOI":"10.1016\/j.archoralbio.2022.105467"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/182186a0","article-title":"Content of Citrulline and Other Amino Acids in a Protein of Hair Follicles","volume":"182","author":"Rogers","year":"1958","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7592851","DOI":"10.1155\/2019\/7592851","article-title":"An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders","volume":"2019","author":"Alghamdi","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gabarrini, G., Heida, R., van Ieperen, N., Curtis, M.A., van Winkelhoff, A.J., and van Dijl, J.M. (2018). Dropping Anchor: Attachment of Peptidylarginine Deiminase via A-LPS to Secreted Outer Membrane Vesicles of Porphyromonas gingivalis. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-27223-5"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, C., Yu, R., and Ding, Y. (2022). Association between Porphyromonas gingivalis and Systemic Diseases: Focus on T Cells-Mediated Adaptive Immunity. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1026457"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"390","DOI":"10.5114\/ceji.2017.72807","article-title":"The Role of Anti-Citrullinated Protein Antibodies (ACPA) in the Pathogenesis of Rheumatoid Arthritis","volume":"42","author":"Kurowska","year":"2017","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_20","first-page":"188","article-title":"Aggregatibacter actinomycetemcomitans: Virulence of Its Leukotoxin and Association with Aggressive Periodontitis","volume":"6","author":"Kelk","year":"2014","journal-title":"Virulence"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sv\u00e4rd, A., LoMartire, R., Martinsson, K., \u00d6hman, C., Kastbom, A., and Johansson, A. (2024). Presence and Immunoreactivity of Aggregatibacter actinomycetemcomitans in Rheumatoid Arthritis. Pathogens, 13.","DOI":"10.3390\/pathogens13050368"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., G\u00f8tzsche, P.C., Ioannidis, J.P.A., Clarke, M., Devereaux, P.J., Kleijnen, J., and Moher, D. (2009). The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration. PLoS Med., 6.","DOI":"10.2427\/5768"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 Statement","volume":"4","author":"Moher","year":"2015","journal-title":"Syst. Rev."},{"key":"ref_24","unstructured":"(2024, August 05). Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration. 4 March 2019, Available online: https:\/\/ntp.niehs.nih.gov\/ntp\/ohat\/pubs\/handbookmarch2019_508.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.prosdent.2022.05.019","article-title":"Development and Validation of a Risk-of-Bias Tool for Assessing In Vitro Studies Conducted in Dentistry: The QUIN","volume":"131","author":"Sheth","year":"2022","journal-title":"J. Prosthet. Dent."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bereta, G.P., Strzelec, K., \u0141azarz-Bartyzel, K., Dziedzic-Kowalska, A., Nowakowska, Z., Krutyho\u0142owa, A., Bielecka, E., Kantyka, T., Grabiec, A.M., and Kaczmarzyk, T. (2024). Identification of a New Genetic Variant (G231N, E232T, N235D) of Peptidylarginine Deiminase from P. gingivalis in Advanced Periodontitis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1355357"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00343-20","DOI":"10.1128\/JB.00343-20","article-title":"PPAD Activity Promotes Outer Membrane Vesicle Biogenesis and Surface Translocation by Porphyromonas gingivalis","volume":"203","author":"Vermilyea","year":"2021","journal-title":"J. Bacteriol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1074\/mcp.RA119.001700","article-title":"Citrullinome of Porphyromonas gingivalis Outer Membrane Vesicles: Confident Identification of Citrullinated Peptides","volume":"19","author":"Larsen","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Aliko, A., Kami\u0144ska, M., Bergum, B., Gawron, K., Benedyk, M., Lamont, R.J., Malicki, S., Delaleu, N., Potempa, J., and Mydel, P. (2018). Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-32603-y"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s13075-020-02348-z","article-title":"Effect of Porphyromonas gingivalis Infection on Gut Dysbiosis and Resultant Arthritis Exacerbation in Mouse Model","volume":"22","author":"Hamamoto","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Vermilyea, D.M., Ottenberg, G.K., and Davey, M.E. (2019). Citrullination Mediated by PPAD Constrains Biofilm Formation in P. gingivalis Strain 381. Npj Biofilms Microbiomes, 5.","DOI":"10.1038\/s41522-019-0081-x"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e01704-18","DOI":"10.1128\/mBio.01704-18","article-title":"A Secreted Bacterial Peptidylarginine Deiminase Can Neutralize Human Innate Immune Defenses","volume":"9","author":"Stobernack","year":"2018","journal-title":"mBio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12967-018-1588-2","article-title":"Increased Citrullination and Expression of Peptidylarginine Deiminases Independently of P. gingivalis and A. actinomycetemcomitans in Gingival Tissue of Patients with Periodontitis","volume":"16","author":"Eriksson","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1177\/1753425917716266","article-title":"Porphyromonas gingivalis and Its LPS Differentially Regulate the Expression of Peptidyl Arginine Deiminases in Human Chondrocytes","volume":"23","author":"Elkaim","year":"2017","journal-title":"Innate Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"369ra176","DOI":"10.1126\/scitranslmed.aaj1921","article-title":"Aggregatibacter actinomycetemcomitans-Induced Hypercitrullination Links Periodontal Infection to Autoimmunity in Rheumatoid Arthritis","volume":"8","author":"Konig","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4532","DOI":"10.1021\/acs.jproteome.6b00634","article-title":"Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis","volume":"15","author":"Stobernack","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1136\/annrheumdis-2015-207656","article-title":"Crystal Structure of Porphyromonas gingivalis Peptidylarginine Deiminase: Implications for Autoimmunity in Rheumatoid Arthritis","volume":"75","author":"Montgomery","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s12967-015-0625-7","article-title":"Association of Levels of Antibodies Against Citrullinated Cyclic Peptides and Citrullinated \u03b1-Enolase in Chronic and Aggressive Periodontitis as a Risk Factor of Rheumatoid Arthritis: A Case-Control Study","volume":"13","author":"Reichert","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"32481","DOI":"10.1074\/jbc.C114.617142","article-title":"Peptidyl Arginine Deiminase from Porphyromonas gingivalis Abolishes Anaphylatoxin C5a Activity","volume":"289","author":"Bielecka","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1128\/IAI.01624-14","article-title":"Citrullination and Proteolytic Processing of Chemokines by Porphyromonas gingivalis","volume":"82","author":"Moelants","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.anaerobe.2013.07.001","article-title":"Porphyromonas gingivalis Peptidylarginine Deiminase Substrate Specificity","volume":"23","author":"Abdullah","year":"2013","journal-title":"Anaerobe"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Maresz, K.J., Hellvard, A., Sroka, A., Adamowicz, K., Bielecka, E., Koziel, J., Gawron, K., Mizgalska, D., Marcinska, K.A., and Benedyk, M. (2013). Porphyromonas gingivalis Facilitates the Development and Progression of Destructive Arthritis through Its Unique Bacterial Peptidylarginine Deiminase (PAD). PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003627"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1002\/art.27552","article-title":"Peptidylarginine Deiminase from Porphyromonas gingivalis Citrullinates Human Fibrinogen and \u03b1-Enolase: Implications for Autoimmunity in Rheumatoid Arthritis","volume":"62","author":"Wegner","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1600-051X.1998.tb02419.x","article-title":"Microbial Complexes in Subgingival Plaque","volume":"25","author":"Socransky","year":"1998","journal-title":"J. Clin. Periodontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nrmicro2873","article-title":"The Keystone-Pathogen Hypothesis","volume":"10","author":"Hajishengallis","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/clinids\/11.1.46","article-title":"Infection Due to Actinobacillus actinomycetemcomitans: 15 Cases and Review","volume":"11","author":"Kaplan","year":"1989","journal-title":"Rev. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1128\/JCM.00729-13","article-title":"A Consortium of Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, and Filifactor alocis Is Present in Sites Prior to Bone Loss in a Longitudinal Study of Localized Aggressive Periodontitis","volume":"51","author":"Fine","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"de Jong, C., Bikker, F.J., Gibbs, S., and Krom, B.P. (2023). Mechanisms of Porphyromonas gingivalis to Translocate over the Oral Mucosa and Other Tissue Barriers. J. Oral Microbiol., 15.","DOI":"10.1080\/20002297.2023.2205291"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1128\/MMBR.00031-09","article-title":"Virulence and Immunomodulatory Roles of Bacterial Outer Membrane Vesicles","volume":"74","author":"Ellis","year":"2010","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1574-6968.1998.tb13049.x","article-title":"On the Origin of Membrane Vesicles in Gram-Negative Bacteria","volume":"163","author":"Zhou","year":"1998","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/mbo3.221","article-title":"Fimbriae-Mediated Outer Membrane Vesicle Production and Invasion of Porphyromonas gingivalis","volume":"4","author":"Mantri","year":"2014","journal-title":"Microbiol. Open"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13054-016-1250-4","article-title":"The Role of Neutrophils in Immune Dysfunction during Severe Inflammation","volume":"20","author":"Leliefeld","year":"2016","journal-title":"Crit. Care"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.arr.2013.05.006","article-title":"Phagocyte Dysfunction, Tissue Aging and Degeneration","volume":"12","author":"Li","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Deng, Q., Pan, B., Alam, H.B., Liang, Y., Wu, Z., Liu, B., Mor-Vaknin, N., Duan, X., Williams, A.M., and Tian, Y. (2020). Citrullinated Histone H3 as a Therapeutic Target for Endotoxic Shock in Mice. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02957"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pan, B., Alam, H.B., Chong, W., Mobley, J., Liu, B., Deng, Q., Liang, Y., Wang, Y., Chen, E., and Wang, T. (2017). CitH3: A Reliable Blood Biomarker for Diagnosis and Treatment of Endotoxic Shock. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09337-4"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1161\/CIRCRESAHA.119.314581","article-title":"Extracellular DNA NET-Works with Dire Consequences for Health","volume":"125","author":"Sorvillo","year":"2019","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1111\/cmi.12655","article-title":"Mechanisms of Outer Membrane Vesicle Entry into Host Cells","volume":"18","author":"Krachler","year":"2016","journal-title":"Cell Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.2174\/138161209788682325","article-title":"The Roles of Antimicrobial Peptides in Innate Host Defense","volume":"15","author":"Diamond","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Duarte-Mata, D.I., and Salinas-Carmona, M.C. (2023). Antimicrobial Peptides\u2019 Immune Modulation Role in Intracellular Bacterial Infection. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1119574"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"974","DOI":"10.4049\/jimmunol.2001374","article-title":"Citrullination Alters the Antibacterial and Anti-Inflammatory Functions of the Host Defense Peptide Canine Cathelicidin K9CATH In Vitro","volume":"207","author":"Padhi","year":"2021","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1159\/000357780","article-title":"The Biological Functions, Structure, and Sources of CXCL10 and Its Outstanding Role in the Pathophysiology of Multiple Sclerosis","volume":"21","author":"Vazirinejad","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1182\/blood-2008-04-149039","article-title":"Citrullination of CXCL10 and CXCL11 by Peptidylarginine Deiminase: A Naturally Occurring Posttranslational Modification of Chemokines and New Dimension of Immunoregulation","volume":"112","author":"Loos","year":"2008","journal-title":"Blood"},{"key":"ref_63","first-page":"456","article-title":"The Role of Interleukin-8 in Inflammation and Mechanisms of Regulation","volume":"64","author":"Bickel","year":"1993","journal-title":"J. Periodontol."},{"key":"ref_64","first-page":"2060","article-title":"CXCL8 and Its Cognate Receptors CXCR1\/CXCR2 in Primary Myelofibrosis","volume":"109","author":"Vermeersch","year":"2024","journal-title":"Haematologica"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1084\/jem.20080305","article-title":"Citrullination of CXCL8 by Peptidylarginine Deiminase Alters Receptor Usage, Prevents Proteolysis, and Dampens Tissue Inflammation","volume":"205","author":"Proost","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1093\/eurheartj\/ehae205","article-title":"Myocardial Reperfusion Injury Exacerbation due to ALDH2 Deficiency Is Mediated by Neutrophil Extracellular Traps and Prevented by Leukotriene C4 Inhibition","volume":"45","author":"Yang","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1182\/blood-2013-07-514992","article-title":"VWF-Mediated Leukocyte Recruitment with Chromatin Decondensation by PAD4 Increases Myocardial Ischemia\/Reperfusion Injury in Mice","volume":"123","author":"Savchenko","year":"2014","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.bbrc.2018.07.069","article-title":"Citrullinated Histone 3 Causes Endothelial Barrier Dysfunction","volume":"503","author":"Meegan","year":"2018","journal-title":"Biochem. Biophys. Res. 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