Combined patient and animal model studies implicate microbiota-triggered T _H 17 cells as disease drivers and therapeutic targets in periodontitis.

Fibrin gums up the works: Plasmin is an abundant plasma protease that cleaves and deactivates the clot-associated protein fibrin. Human deficiencies in plasmin and its inactive proenzyme form, plasminogen (PLG), cause severe inflammation in mucosal tissues such as the mouth and eyes. Silva et al . report that, like humans, mice lacking plasminogen accumulate extravascular fibrin and develop an oral pathology that phenocopies human ligneous periodontitis (see the Perspective by Vicanolo and Hidalgo). The excess fibrin activates neutrophils through the αMβ2 (Mac-1) integrin receptor, which triggers the production of reactive oxygen species and neutrophil extracellular traps. Additionally, certain human polymorphisms in the PLG gene were found to be associated with increased likelihood of developing periodontitis, suggesting that fibrin–neutrophil interactions may be an attractive target for future treatments of this prevalent disease. —STS

Type 1 immunity gives fungi a foothold: Type 17 immune responses play a vital role against fungal infections of the mucosa. It remains unclear whether other types of immune responses can also contribute to host defense against these pathogens. The yeast Candida albicans prominently infects patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), an inherited disease caused by loss-of-function mutations in the AIRE gene. Break et al. report that the oral susceptibility of Aire -deficient mice to C. albicans is not due to aberrant type 17 responses. Rather, the overproduction of interferon-γ by local CD4 ⁺ and CD8 ⁺ T cells in these mice disrupts the epithelial barrier, which increases susceptibility to C. albicans invasion. Similar type 1 immune pathways are operational in APECED patients. Inhibition of interferon-γ or the JAK-STAT signaling pathway in mice ameliorates disease symptoms, suggesting potential future therapeutic interventions for certain classes of fungal disease. Science , this issue p. eaay5731

Background: This Consensus Workshop dealt with diagnostic methodologies in the context of surveillance, screening, assessment of stage and grade, prognosis, monitoring and prediction of periodontal status. Several elements provided the impetus for the workshop, including the limited quality of available research on diagnostic tests, the rapid development of new technologies, the implementation of the 2018 classification and the declarations of the World Health Organisation on diagnosis and oral health. Aim: To update and evaluate the evidence on diagnostic methods, considering recent advances in knowledge and the implementation of the 2018 classification. Methods: The European Workshop Committee of the European Federation of Periodontology guided the development of a consensus report after commissioning eight systematic reviews within three working groups. The reviews were discussed during the in‐person consensus meeting involving 70 participants from 21 different countries. Results: Working Group 1 discussed innovations in traditional diagnostic approaches, justified manual probing as the reference standard and assessed the value of image‐based methods. Working Group 2 analysed diagnostic tests based on microbial and host biomarkers and genetic diagnostic tests. Working Group 3 covered emerging technologies to be used within dental and non‐dental clinical settings, focusing principally on the impact of questionnaire‐based assessments and artificial intelligence systems (AIS) in interpreting different data modalities. Conclusion: Although manual periodontal probing is firmly established as the reference standard, additional approaches based on imaging, biomarkers, host genetics, questionnaires and the development of emerging applied data science methods (e.g., AIS) are increasingly integrated in periodontal diagnostics.

Commensal microbiomes exert critical functions at barrier sites. In particular, establishment of the commensal microbiome after birth dictates immune functionality and tissue homeostasis at mucosal surfaces. To investigate the establishment and stability of the oral mucosal microbiome in mice, we evaluated oral microbiome communities shortly after birth, through adulthood, and up to 1 y of life in a controlled manner, using sequential oral samples from the same mice over time. We further evaluated transmissibility of oral microbiomes from parents and during cohousing experiments and evaluated susceptibility to oral inflammatory disease in mice harboring distinct microbiomes. Our work reveals basic principles in the establishment and stability of a health-associated oral microbiome after birth and provides insights that may be important for host-microbiome experimentation in animal models.