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Veterinary Research Jun 2024Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance...
Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis (S. suis), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae, FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis. In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis. Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.
Topics: Streptococcus suis; Galactose; Quorum Sensing; Virulence; Animals; Bacterial Capsules; Lactones; Streptococcal Infections; Homoserine; Polysaccharides, Bacterial
PubMed: 38886823
DOI: 10.1186/s13567-024-01335-5 -
Scientific Reports Jun 2024The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis...
The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis that serve as biological and structural scaffolds for the development of the dermal tissue. To investigate the dermal structure, the current study used morphological and immunological techniques. TCs identified by TEM. They had a cell body and unique podomeres and podoms. They formed a 3D network spread throughout the dermis. Homocellular contact established between them, as well as heterocellular contacts with other cells. Immunohistochemical techniques using specific markers for TCss CD34, CD117, and VEGF confirmed TC identification. TCs represent the major interstitial component in the dermal tissue. They established a 3D network, enclosing other cells and structures. Expression of VEGF by TC promotes angiogenesis. TCs establish cellular contact with sprouting endothelial cells. At the site of cell junction with TCs, cytoskeletal filaments identified and observed to form the pseudopodium core that projects from endothelial cells. TCs had proteolytic properties that expressed MMP-9, CD68, and CD21. Proteolytic activity aids in the removal of components of the extracellular matrix and the phagocytosis of degraded remnants to create spaces to facilitate the development of new dermal structures. In conclusion, TCs organized the scaffold for the development of future dermal structures, including fibrous components and skin appendages. Studying dermal TCs would be interested in the possibility of developing therapeutic strategies for treating different skin disorders and diseases.
Topics: Telocytes; Immunohistochemistry; Dermis; Humans; Antigens, CD34; Animals; Vascular Endothelial Growth Factor A; Antigens, CD; Matrix Metalloproteinase 9; Endothelial Cells; Antigens, Differentiation, Myelomonocytic; CD68 Molecule
PubMed: 38886354
DOI: 10.1038/s41598-024-63802-5 -
Research Square Jun 2024Microglia are the resident immune cells of the central nervous system (CNS). We and others have shown that the inflammatory response of microglia is partially regulated...
Microglia are the resident immune cells of the central nervous system (CNS). We and others have shown that the inflammatory response of microglia is partially regulated by the immunoproteasome, an inducible form of the proteasome responsible for the generation of major histocompatibility complex (MHC) class I epitopes. While the role of the proteasome in the adaptive immune system is well established, emerging evidence suggests the immunoproteasome may have discrete functions in the innate immune response. Here, we show that inhibiting the immunoproteasome reduces the IFNγ-dependent induction of complement activator C1q, suppresses phagocytosis, and alters the cytokine expression profile in a microglial cell line and microglia derived from human inducible pluripotent stem cells. Moreover, we show that the immunoproteasome regulates the degradation of IκBα, a modulator of NF-κB signaling. Finally, we demonstrate that NADH prevents induction of the immunoproteasome, representing a potential pathway to suppress immunoproteasome-dependent immune responses.
PubMed: 38883799
DOI: 10.21203/rs.3.rs-4467983/v1 -
Materials Today. Bio Jun 2024Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant...
Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant challenges in pancreatic cancer immunotherapy. In this study, we synthesized core-shell FeO@TiO nanoparticles to act as carriers for loading VISTA monoclonal antibodies to form FeO@TiO@VISTAmAb (FTV). The nanoparticles are designed to target the overexpressed ICIs VISTA in pancreatic cancer, aiming to improve magnetic resonance imaging-guided sonodynamic therapy (SDT)-facilitated immunotherapy. Laser confocal microscopy and flow cytometry results demonstrate that FTV nanoparticles are specifically recognized and phagocytosed by Panc-2 cells. In vivo experiments reveal that ultrasound-triggered TiO SDT can induce tumor immunogenic cell death (ICD) and recruit T-cell infiltration within the tumor microenvironment by releasing damage-associated molecular patterns (DAMPs). Furthermore, ultrasound loosens the dense fibrous stroma surrounding the pancreatic tumor and increases vascular density, facilitating immune therapeutic efficiency. In summary, our study demonstrates that FTV nanoparticles hold great promise for synergistic SDT and immunotherapy in pancreatic cancer.
PubMed: 38883421
DOI: 10.1016/j.mtbio.2024.101106 -
ARYA Atherosclerosis 2023There have been very rare reports on the migration of foreign bodies that are left or implanted in the body, and so far, they have only been reported in the...
There have been very rare reports on the migration of foreign bodies that are left or implanted in the body, and so far, they have only been reported in the gastrointestinal tract and intestines (a process similar to phagocytosis), later manifesting as an obstruction in the lumen. Meanwhile, no such cases have yet been reported in the cardiovascular system. The case reported here is a 14-month-old girl who had undergone pulmonary artery banding (PA band made of PTFE) around the pulmonary artery at the age of 8 months due to severe pulmonary hypertension and failure to thrive. She underwent reoperation six months later for a final treatment. It was discovered that the PA band was no longer around the pulmonary artery and had migrated completely into the pulmonary artery while remaining intact and circular and was drawn into the pulmonary artery in a process similar to phagocytosis. The PA band was removed completely. The uneven surface inside the main pulmonary artery was resected and the artery was repaired end-to-end. A total heart repair surgery was again performed on the patient. No problem was observed in the 2.5-year follow-up after the second surgery. Overall, the authors' case is the first instance of migration of a biologically-neutral foreign body into the cardiovascular system that had occurred six months after the PA-band implantation, and the first case of erosion of a foreign body into the lumen outside the gastrointestinal tract. Although the authors could not find the cause of the presented case, reports on future cases can help find the underlying reason.
PubMed: 38882649
DOI: 10.48305/arya.2023.31062.2714 -
Frontiers in Immunology 2024CD24 is a glycosylphosphatidylinositol-anchored protein that is expressed in a wide range of tissues and cell types. It is involved in a variety of physiological and... (Review)
Review
CD24 is a glycosylphosphatidylinositol-anchored protein that is expressed in a wide range of tissues and cell types. It is involved in a variety of physiological and pathological processes, including cell adhesion, migration, differentiation, and apoptosis. Additionally, CD24 has been studied extensively in the context of cancer, where it has been found to play a role in tumor growth, invasion, and metastasis. In recent years, there has been growing interest in CD24 as a potential therapeutic target for cancer treatment. This review summarizes the current knowledge of CD24, including its structure, function, and its role in cancer. Finally, we provide insights into potential clinical application of CD24 and discuss possible approaches for the development of targeted cancer therapies.
Topics: Humans; CD24 Antigen; Neoplasms; Animals; Molecular Targeted Therapy
PubMed: 38881902
DOI: 10.3389/fimmu.2024.1401528 -
Biochemistry and Biophysics Reports Sep 2024Chimeric antigen receptor (CAR)-modified macrophages are a promising treatment for solid tumor. So far the potential effects of CAR-M cell therapy have rarely been...
Chimeric antigen receptor (CAR)-modified macrophages are a promising treatment for solid tumor. So far the potential effects of CAR-M cell therapy have rarely been investigated in hepatocellular carcinoma (HCC). Glypican-3 (GPC3) is a biomarker for a variety of malignancies, including liver cancer, which is not expressed in most adult tissues. Thus, it is an ideal target for the treatment of HCC. In this study, we engineered mouse macrophage cells with CAR targeting GPC3 and explored its therapeutic potential in HCC. First, we generated a chimeric adenoviral vector (Ad5f35) delivering an anti-GPC3 CAR, Ad5f35-anti-GPC3-CAR, which using the CAR construct containing the scFv targeting GPC3 and CD3ζ intracellular domain. Phagocytosis and killing effect indicated that macrophages transduced with Ad5f35-anti-GPC3-CAR (GPC3 CAR-Ms) exhibited antigen-specific phagocytosis and tumor cell clearance in vitro, and GPC3 CAR-Ms showed significant tumor-killing effects and promoted expression of pro-inflammatory (M1) cytokines and chemokines. In 3D NACs-origami spheroid model of HCC, CAR-Ms were further demonstrated to have a significant tumor killing effect. Together, our study provides a new strategy for the treatment of HCC through CAR-M cells targeting GPC3, which provides a basis for the research and treatment of hepatocellular carcinoma.
PubMed: 38881757
DOI: 10.1016/j.bbrep.2024.101741 -
Biochemistry. Biokhimiia May 2024Phagocytosis is an essential innate immunity function in humans and animals. A decrease in the ability to phagocytize is associated with many diseases and aging of the...
Phagocytosis is an essential innate immunity function in humans and animals. A decrease in the ability to phagocytize is associated with many diseases and aging of the immune system. Assessment of phagocytosis dynamics requires quantification of bacteria inside and outside the phagocyte. Although flow cytometry is the most common method for assessing phagocytosis, it does not include visualization and direct quantification of location of bacteria. Here, we used double-labeled Escherichia coli cells to evaluate phagocytosis by flow cytometry (cell sorting) and confocal microscopy, as well as employed image cytometry to provide high-throughput quantitative and spatial recognition of the double-labeled E. coli associated with the phagocytes. Retention of pathogens on the surface of myeloid and lymphoid cells without their internalization was suggested to be an auxiliary function of innate immunity in the fight against infections. The developed method of bacterial labeling significantly increased the accuracy of spatial and quantitative measurement of phagocytosis in whole blood and can be recommended as a tool for phagocytosis assessment by image cytometry.
Topics: Phagocytosis; Escherichia coli; Flow Cytometry; Humans; Microscopy, Confocal; Staining and Labeling; Image Cytometry; Animals
PubMed: 38880652
DOI: 10.1134/S0006297924050122 -
ELife Jun 2024Developmental signaling pathways associated with growth factors such as TGFb are commonly dysregulated in melanoma. Here we identified a human TGFb enhancer specifically...
Developmental signaling pathways associated with growth factors such as TGFb are commonly dysregulated in melanoma. Here we identified a human TGFb enhancer specifically activated in melanoma cells treated with TGFB1 ligand. We generated stable transgenic zebrafish with this TGFb Induced Enhancer driving green fluorescent protein (). was not expressed in normal melanocytes or early melanomas but was expressed in spatially distinct regions of advanced melanomas. Single-cell RNA-sequencing revealed that melanoma cells down-regulated interferon response while up-regulating a novel set of chronic TGFb target genes. ChIP-sequencing demonstrated that AP-1 factor binding is required for activation of chronic TGFb response. Overexpression of , a chromatin remodeler associated with tumor spreading, showed activation of TGFb signaling in early melanomas. Confocal imaging and flow cytometric analysis showed that macrophages localize to regions and preferentially phagocytose melanoma cells compared to melanoma cells. This work identifies a TGFb induced immune response and demonstrates the need for the development of chronic TGFb biomarkers to predict patient response to TGFb inhibitors.
Topics: Zebrafish; Melanoma; Animals; Humans; Signal Transduction; Animals, Genetically Modified; Green Fluorescent Proteins; Transforming Growth Factor beta1; Cell Line, Tumor; Genes, Reporter; Transforming Growth Factor beta; Gene Expression Regulation, Neoplastic
PubMed: 38874379
DOI: 10.7554/eLife.83527 -
Frontiers in Immunology 2024Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and... (Review)
Review
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and replication. Cholesterol is the main carbon source during the infection process of Mtb. Cholesterol metabolism in macrophages is tightly associated with cell functions such as phagocytosis of pathogens, antigen presentation, inflammatory responses, and tissue repair. Research has shown that Mtb infection increases the uptake of low-density lipoprotein (LDL) and cholesterol by macrophages, and enhances cholesterol synthesis in macrophages. Excessive cholesterol is converted into cholesterol esters, while the degradation of cholesterol esters in macrophages is inhibited by Mtb. Furthermore, Mtb infection suppresses the expression of ATP-binding cassette (ABC) transporters in macrophages, impeding cholesterol efflux. These alterations result in the massive accumulation of cholesterol in macrophages, promoting the formation of lipid droplets and foam cells, which ultimately facilitates the persistent survival of Mtb and the progression of tuberculosis (TB), including granuloma formation, tissue cavitation, and systemic dissemination. Mtb infection may also promote the conversion of cholesterol into oxidized cholesterol within macrophages, with the oxidized cholesterol exhibiting anti-Mtb activity. Recent drug development has discovered that reducing cholesterol levels in macrophages can inhibit the invasion of Mtb into macrophages and increase the permeability of anti-tuberculosis drugs. The development of drugs targeting cholesterol metabolic pathways in macrophages, as well as the modification of existing drugs, holds promise for the development of more efficient anti-tuberculosis medications.
Topics: Mycobacterium tuberculosis; Cholesterol; Humans; Macrophages; Tuberculosis; Animals; Host-Pathogen Interactions; Antitubercular Agents; Lipid Metabolism
PubMed: 38873598
DOI: 10.3389/fimmu.2024.1402024