IL-10 and IL-10 receptor overexpression in oral giant cell lesions

Objective: Central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) occur in the jaws and contain osteoclast-like giant cells and mononuclear cells positive for the macrophage marker CD68. The participation of immune-inflammatory mechanisms has been proposed in the lesions development. As IL-10 is one of the most important anti-inflammatory cytokines and it is also an inhibitory cytokine to macrophage function and bone resorption, the purpose of the present study was to investigate its expression together with its receptor (IL-10R?) in CGCL and PGCL. Study Design: Six fragments of CGCL and seven fragments of PGCL were obtained by surgical excision. Frozen specimens were cut and subjected to immunofluorescence staining using fluorescent-labeled anti-CD68, anti-IL-10, and anti-IL-10R? monoclonal antibodies. Microscopic analyses were performed and the percentage of positive mononuclear and giant cells for each parameter was obtained. Results: Our results revealed that all giant cells from CGCL and PGCL were CD68+ and IL-10R?+ and that the majority was also positive for IL-10. More than 50% of the mononuclear cells from both lesions expressed IL-10R? and the majority of these cells were CD68+ and IL-10+. Conclusion: Considering that IL-10 has inhibitory effects on the pathologic processes related to the development of the oral giant cell lesions, the high frequencies of cells producing this cytokine seems contradictory to these lesions growth. Investigation about the production of inflammatory cytokines as well as the IL-10 signaling pathways in oral giant cell lesions is required to elucidate the immunopathology of CGCL and PGCL. © Medicina Oral S. L

Activation of Human CD11b+ B1 B-Cells by Trypanosoma cruzi-Derived Proteins Is Associated With Protective Immune Response in Human Chagas Disease

B-cells mediate humoral adaptive immune response via the production of antibodies and cytokines, and by inducing T-cell activation. These functions can be attributed to distinct B-cell subpopulations. Infection with Trypanosoma cruzi, the causative agent of Chagas disease, induces a polyclonal B-cell activation and lytic antibody production, critical for controlling parasitemia. Individuals within the chronic phase of Chagas disease may remain in an asymptomatic form (indeterminate), or develop severe cardiomyopathy (cardiac form) that can lead to death. Currently, there is no effective vaccine to prevent Chagas disease, and no treatment to halt the development of the cardiomyopathy once it is installed. The pathology associated with cardiac Chagas disease is a result of an inflammatory reaction. Thus, discovering characteristics of the host's immune response that favor the maintenance of favorable heart function may unveil important immunotherapeutic targets. Given the importance of B cells in antibody production and parasite control, we investigated T. cruzi-derived antigenic fractions responsible for B-cell activation and whether frequencies and functional characteristics of B-cell subpopulations are associated with different clinical outcomes of human Chagas disease. We stimulated cells from indeterminate (I) and cardiac (C) Chagas patients, as well as non-infected individuals (NI), with T. cruzi-derived protein- (PRO), glycolipid- (GCL) and lipid (LIP)-enriched fractions and determined functional characteristics of B-cell subpopulations. Our results showed that the frequency of B-cells was similar amongst groups. PRO, but not GCL nor LIP, led to an increased frequency of B1 B-cells in I, but not C nor NI. Although stimulation with PRO induced higher TNF expression by B1 B-cells from C and I, as compared to NI, it induced expression of IL-10 in cells from I, but not C. Stimulation with PRO induced an increased frequency of the CD11b+ B1 B-cell subpopulation, which was associated with better cardiac function. Chagas patients displayed increased IgM production, and activation of gamma-delta T-cells, which have been associated with B1 B-cell function. Our data showed that PRO activates CD11b+ B1 B-cells, and that this activation is associated with a beneficial clinical status. These findings may have implications in designing new strategies focusing on B-cell activation to prevent Chagas disease cardiomyopathy

Composite-derived monomers affect cell viability and cytokine expression in human leukocytes stimulated with Porphyromonas gingivalis

Objectives:  Dental composites release unreacted resin monomers into the oral environment, even after polymerization. Periodontal cells are, therefore, exposed to substances that potentially elicit the immune inflammatory response. The underlying molecular mechanisms associated with the interaction between resin monomers and human immune cells found in the gingival crevicular fluid are not fully understood yet. This study investigated the ability of bisphenol A-glycidyl methacrylate (BISGMA), urethane dimethacrylate (UDMA) and triethylene glycol dimethacrylate (TEGDMA) to induce apoptosis and cytokine release by human leukocytes stimulated with a periodontal pathogen. Methodology: Peripheral blood mononuclear cells (PBMC) from 16 healthy individuals were included in this study. To determine the toxicity, the PBMC were incubated for 20 hours, with monomers, for the analysis of cell viability using MTT assay. To evaluate cell death in the populations of monocytes and lymphocytes, they were exposed to sub-lethal doses of each monomer and of heat-inactivated Porphyromonas gingivalis (P. gingivalis) for 5 hours. Secretions of IL-1β, IL-6, IL-10 and TNF-α were determined by ELISA after 20 hours. Results: UDMA and TEGDMA induced apoptosis after a short-time exposure. Bacterial challenge induced significant production of IL-1β and TNF-α (p<0.05). TEGDMA reduced the bacterial-induced release of IL-1β and TNF-α, whereas UDMA reduced IL-1β release (p<0.05). These monomers did not affect IL-10 and IL-6 secretion. BISGMA did not significantly interfere in cytokine release.  Conclusions: These results show that resin monomers are toxic to PBMC in a dose-dependent manner, and may influence the local immune inflammatory response and tissue damage mechanisms via regulation of bacterial-induced IL-1β and TNF-α secretion by PBMC

Clinical aspects of Chagas disease and implications for novel therapies.

The interaction between the protozoan parasite Trypanosoma cruzi and the human host dates back 9,000 years, as demonstrated by molecular analysis of material obtained from Andean mummies indicating the presence of the parasite?s kinetoplast DNA in populations from Chile and Peru. This long-established interaction, which persists today, demonstrates that T. cruzi has established a very well adapted relationship with the human host. From the point of view of a host?parasite relationship, this is desirable; however, such a high degree of adaptation is perhaps the foundation for many of the unknowns that surround this disease. Unveiling of the immunological mechanisms that underlie the establishment of pathology, identification of parasite-associated factors that determine strain-differential tissue tropism, discovery of host genetic elements that influence the development of different clinical forms of the disease, and understanding environmental factors that may influence the host?parasite interactions are some of the key questions that remain to be answered. The response to these questions will aid in addressing some of the current challenges in Chagas disease: fulfilling the need for efficient diagnosis, developing effective prophylactic measures, discovering effective therapeutics, and finding methods to control disease progression

Imunologia da retinocoroidite toxoplásmica

A infecção pelo Toxoplasma gondii é uma importante causa de doença ocular, tanto em indivíduos imunocomprometidos como em imunocompetentes. A patogênese da destruição retinocoroidiana associada a essa infecção ainda não está totalmente esclarecida. Nesta revisão, discute-se o papel do sistema imune no controle da infecção pelo Toxoplasma, especialmente, no olho