Phagocytic Dendritic Cells Research Articles

Immune and inflammatory responses of human macrophages, dendritic cells, and T-cells in presence of micro- and nanoplastic of different types and sizes

Environmental pollution by microplastics (MPs) is a growing concern regarding their impact on aquatic and terrestrial systems and human health. Typical exposure routes of MPs are dermal contact, digestion, and inhalation. Recent in vitro and in vivo studies observed alterations in immunity after MPs exposure, but systemic studies using primary human immune cells are scarce. In our investigation, we addressed the effect of polystyrene (PS) and poly methyl methacrylate (PMMA) in three different sizes (50–1100 nm) as well as amino-modified PS (PS-NH2; 50 nm) on cells of the adaptive and innate immune system. T-cells isolated from human peripheral blood mononuclear cells (PBMCs) were least affected regarding the cytotoxicity but displayed increased activation marker expression after 72 h, and strongly modulated cytokine secretion patterns. Conversely, phagocytic dendritic cells and macrophages derived from isolated monocytes were highly sensitive to pristine MPs. Their marker expression suggested a downregulation of the inflammatory phenotypes indicative of M2 macrophage induction after MPs exposure for 24 h. Our results showed that even pristine MPs affected immune cell function and inflammatory phenotype dependent on MPs polymers, size, and immune cell type.

Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells--A Key Role for Heat-Shock Protein 70 and Receptor CD91.

Immune responses contribute to the success of radiotherapy of solid tumors; however, the mechanism of triggering CD8(+) T-cell responses is poorly understood. Antigen cross-presentation from tumor cells by dendritic cells (DC) is a likely dominant mechanism to achieve CD8(+) T-cell stimulation. We established a cross-presentation model in which DCs present a naturally expressed oncofetal tumor antigen (5T4) from irradiated DU145 prostate cancer cells to 5T4-specific T cells. The aim was to establish which immunogenic signals are important in radiation-induced cross-presentation. Radiation (12 Gy) caused G2-M cell-cycle arrest and cell death, increased cellular 5T4 levels, high-mobility protein group-B1 (HMGB1) release, and surface calreticulin and heat-shock protein-70 (Hsp70) expression in DU145 cells. DCs phagocytosed irradiated tumor cells efficiently, followed by upregulation of CD86 on phagocytic DCs. CD8(+) 5T4-specific T cells, stimulated with these DCs, proliferated and produced IFNγ. Inhibition of HMGB1 or the TRIF/MyD88 pathway only had a partial effect on T-cell stimulation. Unlike previous investigators, we found no evidence that DCs carrying Asp299Gly Toll-like receptor-4 (TLR4) single-nucleotide polymorphism had impaired ability to cross-present tumor antigen. However, pretreatment of tumor cells with Hsp70 inhibitors resulted in a highly statistically significant and robust prevention of antigen cross-presentation and CD86 upregulation on DCs cocultured with irradiated tumor cells. Blocking the Hsp70 receptor CD91 also abolished cross-presentation. Together, the results from our study demonstrate that irradiation induces immunologically relevant changes in tumor cells, which can trigger CD8(+) T-cell responses via a predominantly Hsp70-dependent antigen cross-presentation process.

Salmonella-host interactions - modulation of the host innate immune system.

Salmonella enterica (S. enterica) are Gram-negative bacteria that can invade a broad range of hosts causing both acute and chronic infections. This phenotype is related to its ability to replicate and persist within non-phagocytic host epithelial cells as well as phagocytic dendritic cells and macrophages of the innate immune system. Infection with S. enterica manifests itself through a broad range of clinical symptoms and can result in asymptomatic carriage, gastroenteritis, systemic disease such as typhoid fever and in severe cases, death (1). Exposure to S. enterica serovars Typhi and Paratyphi exhibits clinical symptoms including diarrhea, fatigue, fever, and temperature fluctuations. Other serovars such as the non-typhoidal Salmonella (NTS), of which there are over 2,500, are commonly contracted as, but not limited to, food-borne sources causing gastrointestinal symptoms, which include diarrhea and vomiting. The availability of complete genome sequences for many S. enterica serovars has facilitated research into the genetic determinants of virulence for this pathogen. This work has led to the identification of important bacterial components, including flagella, type III secretion systems, lipopolysaccharides, and Salmonella pathogenicity islands, all of which support the intracellular life cycle of S. enterica. Studies focusing on the host–pathogen interaction have provided insights into receptor activation of the innate immune system. Therefore, characterizing the host–S. enterica interaction is critical to understand the pathogenicity of the bacteria in a clinically relevant context. This review outlines salmonellosis and the clinical manifestations between typhoidal and NTS infections as well as discussing the host immune response to infection and the models that are being used to elucidate the mechanisms involved in Salmonella pathogenicity.

Abstract 4290: Visualizing immune surveillance in lung metastasis progression

Abstract As stipulated by the Paget and Fuchs’ “seed and soil” analogy, the establishment of metastases depends on the microenvironment of target tissue; as such, it also depends on the tissue immunosurveillance system. Anti-tumor immune responses are subdued in advanced tumors by various immune suppressory mechanisms, such as by tumor associated CD4 FoxP3 regulatory T-reg cells. But how immune suppression sets in at the sites of metastasis, and how it could be overcome there remains unclear. Using multiphoton and confocal microscopy, we have visualized the immune cell's dynamics that is triggered by various metastatic cancers in the lungs. We found that single, blood-carried cancer cells that settle in the capillary bed triggered strikingly rapid recruitment of CD11c dendritic cells (DCs), which were heterogeneous. Some of those DCs wrapped around the singular cancer cells while other probed their intracellular content by acquiring tumor-derived vesicles. These phagocytic DCs then carried away their cargo towards the draining lymph nodes, thereby initiating tumor antigen cross-presentation. After 24-48 hours, micrometastases became surrounded by T cells that were highly enriched in T-reg. The motility patterns and cell depletion experiments showed that T-reg largely ignored tumor cells but were attracted by the phagocytic tumor-associated DCs. In result of these interactions, the phagocytic DCs became the foci of highly dynamic three-cell interactions between T-reg and the effector T cells, sequestering most T cells at the tumor margin. In this context, we tested the impact of immunomodulatory therapies. The immune cell dynamics that we uncovered in metastases was responsive to therapeutic immune modulation aimed at the tumor-associated phagocytic DCs and also at Programmed Death (PD-1) pathways. Taken together, our intravital dynamic imaging results highlight the duality of metastasis-associated phagocytic DCs. On the one hand, these cells provide tumor antigen cross-presentation and recruit T cells to nascent secondary tumors, but on the other hand, they aid metastasis progression by promoting early on the contact of tumor-infiltrating T cells with T-reg. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4290. doi:1538-7445.AM2012-4290

Multifunctional Silica Nanocapsule with a Single Surface Hole

Multifunctional silica nanocapsules containing magnetic nanoparticles and fluorescent quantum dots with a single surface hole fabricated by a single-step emulsion-mediated process are described. The silica nanocapsules (see images) are easily internalized by phagocytic dendritic cells and show a high potential as bimodal imaging contrast agents (for fluorescence and magnetic resonance imaging) in vivo as well as in vitro.

Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a single cell level

AbstractAntigen-presenting cells (APCs) from subcutaneous mouse MOPC315 plasmacytoma phagocytosed immunoglobulin G–coated magnetic beads, enabling efficient isolation within 2 hours by magnetic separation (APC-MB). Cell morphology was heterogeneous, with some of the cells having dendrites. The surface phenotype of purified tumor APCs-MB was CD11b+, CD11c+, CD40+, CD80+, CD86+, and MHC class II+. Tumor APCs-MB expressed messenger RNA for fractalkine and ABCD-1 chemokines, and for CC-type chemokine receptors CCR5 and CCR7, indicating the presence of mature dendritic cells (DCs). Visualized at a single cell level within 4 hours after disruption of the tumor, APCs-MB induced rapid Ca++ mobilization in MHC class II–restricted tumor idiotype (Id)–specific cloned CD4+ T cells. In long-term assays, tumor APCs-MB induced proliferation of naive T cells from Id-specific T-cell receptor transgenic mice. The results suggest that tumor APCs-MB represent a heterogeneous cell population that includes myeloid-derived DCs of various stages of maturation. A considerable fraction (≥ 15%) of DCs is spontaneously primed with tumor-specific antigen.