Background: Periodontitis is a chronic inflammatory disease associated with a dysbiotic biofilm. Many pathogens have been related with its progression and severity, one of which is Aggregatibacter actinomycetemcomitans, a Gram-negative bacteria with seven serotypes (a–g) according with the structure of its LPS, with serotype b defined as the most virulent compared with the other serotypes. The aim of this study was to evaluate the response of oral keratinocytes and macrophages to A. actinomycetemcomitans. Methods: Oral keratinocytes (OKF6/TERT2) and macrophages (THP-1) were infected with A. actinomycetemcomitans serotypes a, b and c. The expression of IL-1β, IL-6, IL-8, IL-18, TNF-α, MMP-9, RANKL, TLR-2, TLR-4, TLR-6, thymic stromal lymphopoietin (TSLP), and ICAM-1 was evaluated by qPCR at 2 and 24 h after infection. Results: An increase in the expression of these molecules was induced by all serotypes at both times of infection, with macrophages showing higher levels of expression at 24 h compared to epithelial cells in which the highest levels were observed in the first hours after infection. Conclusions: Keratinocytes and macrophages contribute to the inflammation in periodontitis from the early stages of infection, producing the first waves of cytokines, acting as the first signal for professional immune cell recruitment and modulation of more specific immune responses.

The etiology of gallbladder cancer (GBC) is multifactorial, with chronic inflammation resulting from infections, autoimmune diseases, and lifestyle factors playing a pivotal role. Vitamin D deficiency (VDD) has been implicated in the pathogenesis of autoimmune disorders and various malignancies, including GBC. Research on autoimmune diseases highlights the anti-inflammatory properties of vitamin D, suggesting its potential to mitigate disease progression. In oncology, VDD has similarly been linked to increased inflammation, which may contribute to both the initiation and progression of cancer. A critical component in carcinogenesis, as well as in the immunomodulatory effects of vitamin D in autoimmune conditions, is the balance between T-helper 17 (Th17) cells and regulatory T (Treg) cells. We hypothesize that vitamin D may inhibit epithelial–mesenchymal transition (EMT) in GBC by modulating the spatial distribution of tumor-infiltrating T cells, particularly through the regulation of the Th17/Treg balance at the tumor margins. This Th17/Treg imbalance may act as a mechanistic link between VDD and the progression of GBC carcinogenesis. Investigating the role of an Th17/Treg imbalance as a mediator in VDD-induced EMT in GBC not only provides deeper insights into the pathogenesis of GBC but also sheds light on broader mechanisms relevant to the development of other solid organ cancers, given the expanding recognition of the roles of VDD and Th17/Treg cells in cancer biology.

Recurrent aphthous stomatitis is a common inflammatory condition of the oral mucosa characterized by painful ulcers that heal spontaneously but recur unpre

Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium with seven serotypes (a–g) according to the structure of its LPS, has been defined as one of the most important pathogens in the development of a dysbiotic periodontal biofilm and the onset of periodontitis (an inflammatory chronic disease of the tissues around the teeth), where the serotype b is characterized as the most virulent compared with the other serotypes. The aim of this study was to evaluate the expression of the macrophage polarization markers M0, M1, and M2 against A. actinomycetemcomitans. Methods: THP-1 cells were infected with A. actinomycetemcomitans serotypes a, b, and c. The expression of CD11b, CD4, CD14, and CD68 for M0; IL-6, HLA/DRA, and CXCL10 for M21, and IL-10, CD163, fibronectin-1 or FN1, and CCL17 was evaluated by qPCR at 2 and 24 h after infection. Results: An increase in the expression of these molecules was induced by all serotypes at both times of infection, showing higher levels of expression to the M1 panel at 2 and 24 h compared to other markers. Conclusions: A. actinomycetemcomitans has a role in the macrophage polarization to the M1 phenotype in a non-serotype-dependent manner.