-
Journal of Nanobiotechnology Jun 2024Tumor-associated macrophages (TAMs) are pivotal within the immunosuppressive tumor microenvironment (TME), and recently, have attracted intensive attention for cancer...
Tumor-associated macrophages (TAMs) are pivotal within the immunosuppressive tumor microenvironment (TME), and recently, have attracted intensive attention for cancer treatment. However, concurrently to promote TAMs repolarization and phagocytosis of cancer cells remains challenging. Here, a TAMs-targeted albumin nanoparticles-based delivery system (M@SINPs) was constructed for the co-delivery of photosensitizer IR820 and SHP2 inhibitor SHP099 to potentiate macrophage-mediated cancer immunotherapy. M@SINPs under laser irradiation can generate the intracellular reactive oxygen species (ROS) and facilitate M2-TAMs to an M1 phenotype. Meanwhile, inhibition of SHP2 could block the CD47-SIRPa pathway to restore M1 macrophage phagocytic activity. M@SINPs-mediated TAMs remodeling resulted in the immunostimulatory TME by repolarizing TAMs to an M1 phenotype, restoring its phagocytic function and facilitating intratumoral CTLs infiltration, which significantly inhibited tumor growth. Furthermore, M@SINPs in combination with anti-PD-1 antibody could also improve the treatment outcomes of PD-1 blockade and exert the synergistic anticancer effects. Thus, the macrophage repolarization/phagocytosis restoration combination through M@SINPs holds promise as a strategy to concurrently remodel TAMs in TME for improving the antitumor efficiency of immune checkpoint block and conventional therapy.
Topics: Phagocytosis; Animals; Immunotherapy; Mice; Nanoparticles; Tumor-Associated Macrophages; Tumor Microenvironment; CD47 Antigen; Cell Line, Tumor; Neoplasms; Humans; Reactive Oxygen Species; Mice, Inbred C57BL; Receptors, Immunologic; Female
PubMed: 38890636
DOI: 10.1186/s12951-024-02622-1 -
Molecular Genetics & Genomic Medicine Jun 2024The Triggering Receptor Expressed on Myeloid Cells 2 protein (TREM2) plays a crucial role in various biological processes, including osteoclast differentiation, and... (Review)
Review
BACKGROUND
The Triggering Receptor Expressed on Myeloid Cells 2 protein (TREM2) plays a crucial role in various biological processes, including osteoclast differentiation, and disease-associated microglia (DAM) activation to regulate neuroinflammation, and phagocytosis in the brain. Genetic variations in TREM2 are implicated in neurodegenerative disorders, such as Nasu-hakola disease (NHD), characterized by bone lesions, neuropsychiatric disorders, and early-onset dementia.
METHODS
We studied 3 siblings with suspected NHD. Whole-exome sequencing was conducted on the proband to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants in the two other affected siblings, a healthy sister, and the parents.
RESULTS
We identified a novel homozygous deletion (c.549del; p.(Leu184Serfs*5)) in TREM2. Our literature review reveals 16 TREM2 mutations causing early-onset dementia and bone lesions.
CONCLUSION
These findings, alongside previous research, elucidate the clinical spectrum of TREM2-related diseases, aiding accurate diagnosis and patient care. This knowledge is vital for understanding TREM2-dependent DAM and its involvement in the pathogenesis of neurodevelopmental disorders which can help to develop targeted therapies and improve outcomes for TREM2-affected individuals.
Topics: Female; Humans; Consanguinity; Homozygote; Lipodystrophy; Membrane Glycoproteins; Osteochondrodysplasias; Pedigree; Receptors, Immunologic; Siblings; Subacute Sclerosing Panencephalitis
PubMed: 38888203
DOI: 10.1002/mgg3.2476 -
Expert Review of Vaccines 2024Malaria continues to remain a major global health problem with nearly a quarter of a billion clinical cases and more than 600,000 deaths in 2022. There has been... (Review)
Review
INTRODUCTION
Malaria continues to remain a major global health problem with nearly a quarter of a billion clinical cases and more than 600,000 deaths in 2022. There has been significant progress toward vaccine development, however, poor efficacy of approved vaccines requiring multiple immunizing doses emphasizes the need for continued efforts toward improved vaccines. Progress to date, nonetheless, has provided impetus for malaria elimination.
AREAS COVERED
In this review we will focus on diverse immune mechanisms targeting gametocytes in the human host and gametocyte-mediated malaria transmission via the mosquito vector.
EXPERT OPINION
To march toward the goal of malaria elimination it will be critical to target the process of malaria transmission by mosquitoes, mediated exclusively by the sexual stages, i.e. male, and female gametocytes, ingested from infected vertebrate host. Studies over several decades have established antigens in the parasite sexual stages developing in the mosquito midgut as attractive targets for the development of transmission blocking vaccines (TBVs). Immune clearance of gametocytes in the vertebrate host can synergize with TBVs and directly aid in maintaining effective transmission reducing immune potential.
Topics: Humans; Malaria Vaccines; Animals; Malaria; Vaccine Development; Mosquito Vectors; Plasmodium
PubMed: 38888098
DOI: 10.1080/14760584.2024.2369583 -
American Journal of Physiology. Lung... Jun 2024Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving supplemental oxygen therapy; however,...
Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving supplemental oxygen therapy; however, hyperoxia can induce pulmonary inflammation and cellular damage. Although alveolar macrophages (AMs) are essential for lung immune homeostasis, they become compromised during inflammatory lung injury. To combat this, stem cell-derived alveolar-like macrophages (ALMs) are a prospective therapeutic for lung diseases like ARDS. Using and approaches, we investigated the impact of hyperoxia on murine ALMs during acute inflammation. , ALMs retained their viability, growth and antimicrobial abilities when cultured at 60% O,while they die at 90% O. In contrast, ALMs instilled in mouse lungs remained viable during exposure of mice to 90% O. The ability of the delivered ALMs to phagocytose was not impaired by exposure to 60 or 90% O. Furthermore, ALMs remained immunologically stable in a murine model of LPS-induced lung inflammation when exposed to 60 and 90% O and effectively attenuated the accumulation of CD11b inflammatory cells in the airways. These results support the potential use of ALMs in ARDS patients receiving supplemental oxygen therapy.
PubMed: 38887793
DOI: 10.1152/ajplung.00270.2023 -
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