Journal Article

Editorial: Oral neutrophils - the good, the bad, and the ugly

Vitkov, Ljubomir, Knopf, Jasmin, Herrmann, Martin

2023

Overview

In patients with antithrombotic prophylaxis employing low molecular weight heparins, a possible benefit for periodontitis can be expected, as they reportedly reduce NETs formation and dissociate histones from the chromatin backbone of NETs, as resumed byLiu et al.However, any clinical studies on low molecular weight heparins in periodontitis are lacking.Irwandi et al.summarised that novel and targeted approaches to manipulate neutrophil numbers and functions are warranted within the context of the treatment of periodontitis and also to mitigate its potential impact on other LGI disease. Cxcr2 plays a crucial role in phagocytic ability, reactive oxygen species production, F-actin and α-tubulin levels, and phosphorylation of ERK1/2 and p38 MAPK, impaired PI3K-AKT, NF-κB, TGFβ and IFNγ pathways. [...]Cxcr2 blockers might also be a possible option to attenuate the neutrophil hyper-responsiveness seen in periodontitisDelobel et al. 4 Conclusion Recently, the attention in mucosal inflammatory disease has been shifted from the topical to systemic point of view i.e., from the concept of dental biofilm dysbiosis to that of dysregulated immunity. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. 1LeeJYTsolisRMBäumlerAJ.The microbiome and gut homeostasis.Science(2022)377(6601):eabp9960. doi:10.1126/science.abp9960 2SilvaLMBrenchleyLMoutsopoulosNM.Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis.Immunol Rev(2019)287(1):226–35. doi:10.1111/imr.12724 3SilvaLMDoyleADGreenwell-WildTDutzanNTranCLAbuslemeL.Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier.Science(2021)374(6575):eabl5450. doi:10.1126/science.abl5450 4SørensenOEClemmensenSNDahlSLØstergaardOHeegaardNHGlenthøjA.Papillon-lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses.J Clin Invest(2014)124(10):4539–48. doi:10.1172/JCI76009 5VitkovLHartlDMinnichBHannigM.Janus-faced neutrophil extracellular traps in periodontitis.Front Immunol(2017)8:1404. doi:10.3389/fimmu.2017.01404 6WilliamsDWGreenwell-WildTBrenchleyLDutzanNOvermillerASawayaAP.Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity.Cell(2021)184(15):4090–104 e15. doi:10.1016/j.cell.2021.05.013 7MatthewsJBWrightHJRobertsALing-MountfordNCooperPRChappleILC.Neutrophil hyper-responsiveness in periodontitis.J Dental Res(2007)86(8):718–22. doi:10.1177/154405910708600806 8LiXWangHYuXSahaGKalafatiLIoannidisC.Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities.Cell(2022)185(10):1709–27 e18. doi:10.1016/j.cell.2022.03.043 9GoodridgeHSAhmedSSCurtisNKollmannTRLevyONeteaMG.Harnessing the beneficial heterologous effects of vaccination.Nat Rev Immunol(2016)16(6):392–400. doi:10.1038/nri.2016.43 10NeteaMGGiamarellos-BourboulisEJDomínguez-AndrésJCurtisNvan CrevelRvan de VeerdonkFL.Trained immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection.Cell(2020)181(5):969–77. doi:10.1016/j.cell.2020.04.042 11HajishengallisGLiXDivarisKChavakisT.Maladaptive trained immunity and clonal hematopoiesis as potential mechanistic links between periodontitis and inflammatory comorbidities.Periodontol 2000(2022)89(1):215–30. doi:10.1111/prd.12421 12VitkovLMuñozLEKnopfJSchauerCOberthalerHMinnichB.Connection between periodontitis-induced low-grade endotoxemia and systemic diseases: neutrophils as protagonists and targets.Int J Mol Sci(2021)22(9):4647. doi:10.3390/ijms22094647 13TrindadeDCarvalhoRMachadoVChambroneLMendesJJBotelhoJ.Prevalence of periodontitis in dentate people between 2011 and 2020: a systematic review and meta-analysis of epidemiological studies.J Clin Periodontol(2023)50(5):604–26. doi:10.1111/jcpe.13769 14HajishengallisGChavakisT.Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities.Nat Rev Immunol(2021)21(7):426–40. doi:10.1038/s41577-020-00488-6 15AckermannMAndersHJBilyyRBowlinGLDanielCDe LorenzoR.Patients with COVID-19: in the dark-NETs of neutrophils.Cell Death Differ(2021)28(11):3125–39. doi:10.1038/s41418-021-00805-z 16MaroufNCaiWSaidKNDaasHDiabHChintaVR.Association between periodontitis and severity of COVID-19 infection: a case-control study.J Clin Periodontol(2021)48(4):483–91. doi:10.1111/jcpe.13435 17VitkovLKnopfJKrunićJSchauerCSchoenJMinnichB.Periodontitis-derived dark-NETs in severe covid-19.Front Immunol(2022)13:872695. doi:10.3389/fimmu.2022.872695 18AnJYKernsKAOuelletteARobinsonLMorrisHDKaczorowskiC.Rapamycin rejuvenates oral health in aging mice.Elife(2020)9:e54318. doi:10.7554/eLife.54318

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: 1-Phosphatidylinositol 3-kinase / Actin / Adaptive immunity / AKT protein / Bacterial infections / Cell death / Chromatin / Comorbidity / Conflicts of interest / COVID-19 / CXCR2 protein / Disease prevention / dysbiosis / dysregulated immunity / Epidemiology / Fibrin / Gum disease / Hemopoiesis / Homeostasis / Immune response / Immune system / Immunity / Immunity (Disease) / Immunology / Inflammatory diseases / innate immunity / Leukocytes (neutrophilic) / maladaptive trained immunity / MAP kinase / Molecular weight / Mucosa / Myelopoiesis / Neutrophils / Pathogenesis / Patients / Periodontal diseases / Periodontium / Phagocytes / Phosphorylation / Primary immunodeficiencies / Reactive oxygen species / Severe acute respiratory syndrome coronavirus 2 / systemic low-grade inflammation