Comparative Metabolomics Reveals the Microenvironment of Common T-Helper Cells and Differential Immune Cells Linked to Unique Periapical Lesions

Abstract

Periapical abscesses, radicular cysts, and periapical granulomas are the most frequently identified pathological lesions in the alveolar bone. While little is known about the initiation and progression of these conditions, the metabolic environment and the related immunological behaviors were examined for the first time to model the development of each pathological condition. Metabolites were extracted from each lesion and profiled using gas chromatography-mass spectrometry in comparison with healthy pulp tissue. The metabolites were clustered and linked to their related immune cell fractions. Clusters I and J in the periapical abscess upregulated the expression of MMP-9, IL-8, CYP4F3, and VEGF, while clusters L and M were related to lipophagy and apoptosis in radicular cyst, and cluster P in periapical granuloma, which contains L-(+)-lactic acid and ethylene glycol, was related to granuloma formation. Oleic acid, 17-octadecynoic acid, 1-nonadecene, and L-(+)-lactic acid were significantly the highest unique metabolites in healthy pulp tissue, periapical abscess, radicular cyst, and periapical granuloma, respectively. The correlated enriched metabolic pathways were identified, and the related active genes were predicted. Glutamatergic synapse (16–20),-hydroxyeicosatetraenoic acids, lipophagy, and retinoid X receptor coupled with vitamin D receptor were the most significantly enriched pathways in healthy control, abscess, cyst, and granuloma, respectively. Compared with the healthy control, significant upregulation in the gene expression of CYP4F3, VEGF, IL-8, TLR2 (P < 0.0001), and MMP-9 (P < 0.001) was found in the abscesses. While IL-12A was significantly upregulated in cysts (P < 0.01), IL-17A represents the highest significantly upregulated gene in granulomas (P < 0.0001). From the predicted active genes, CIBERSORT suggested the presence of natural killer cells, dendritic cells, pro-inflammatory M1 macrophages, and anti-inflammatory M2 macrophages in different proportions. In addition, the single nucleotide polymorphisms related to IL-10, IL-12A, and IL-17D genes were shown to be associated with periapical lesions and other oral lesions. Collectively, the unique metabolism and related immune response shape up an environment that initiates and maintains the existence and progression of these oral lesions, suggesting an important role in diagnosis and effective targeted therapy.

Plasma Rich in Growth Factors in the Treatment of Endodontic Periapical Lesions in Adult Patients: 3-Dimensional Analysis Using Cone-Beam Computed Tomography on the Outcomes of Non-Surgical Endodontic Treatment Using A-PRF+ and Calcium Hydroxide: A Retrospective Cohort Study

“…It is interesting to note that in 95% of acute periapical periodontitis IL-8 was detectable in the exudative. This suggests that IL-8 may play a crucial role in the development of those lesions [ 39 ]. In the outer area of apical periodontitis, the macrophages and T lymphocytes are predominant.…”

SARS-CoV-2-free residual proteins mediated phenotypic and metabolic changes in peripheral blood monocytic-derived macrophages in support of viral pathogenesis

“…Furthermore, analysis of the heat maps and hierarchical clustering was conducted to discover probable grouping and patterns in the metabolic coverage. All chemometric statistical analysis was carried out using MetaboAnalyst 5.0 ( http://www.metaboanalyst.ca/ ) [ 21 ] and according to Alaa et al, 2021 [ 22 ].…”

Quantificação de células da resposta imune e inflamatória e de peptídeo antimicrobiano (beta-defensina-3), em cistos radiculares de dentes decíduos e permanentes

“…Nos dentes permanentes, foi possível observar que as lesões pequenas apresentaram mediana de células imunomarcadas de 65,00 (Q1=27,50; Q3=80,00), enquanto esse valor foi de 55,00 (Q1=17,50; Q3=78,75) nas lesões grandes, não apresentando diferença estatisticamente significante (p=0,599) (Figuras 13 e 14). A lesão periapical se inicia quando os micro-organismos, seus produtos/subprodutos e os mediadores inflamatórios ultrapassam o forame apical, atingindo os tecidos circundantes (Altaie et al, 2021). Assim, inicia-se um processo infeccioso, inflamatório, imunológico e osteolítico na região apical e periapical, no qual as respostas imunes e inflamatórias são ativadas (Cavalla et al, 2021), com reabsorção dos tecidos mineralizados (Wang et al, 2022).…”

“…Nesse aspecto, em 1997 Nair já havia definido a lesão periapical como sendo a "intersecção dinâmica entre a infecção do canal radicular e a resposta do hospedeiro". Dentre as lesões periapicais, os abscessos periapicais, os cistos radiculares (de origem inflamatória) e os granulomas periapicais são as mais frequentemente observadas (Altaie et al, 2021).…”

“…Os macrófagos apresentam uma vasta dinâmica de diferenciação, podendo ser polarizados basicamente em tipo M1 (pró-inflamatório) e M2 (anti-inflamatório) (Altaie et al, 2021). A polarização macrofágica do tipo M1 está relacionada ao processo de combate aos patógenos e destruição tecidual, por meio da produção de citocinas pró-inflamatórias como IL-1β, TNF-α, IL-12 e IL-18.…”