-
Cell Communication and Signaling : CCS Jul 2023The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH)....
BACKGROUND
The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia.
METHODS
We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms.
RESULTS
In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP.
CONCLUSION
P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.
Topics: Humans; Microglia; Subarachnoid Hemorrhage; Phagocytosis; Autophagy; Inflammation; Death-Associated Protein Kinases
PubMed: 37480108
DOI: 10.1186/s12964-023-01173-6 -
Immunity, Inflammation and Disease Dec 2021Neutrophils play multiple roles in acute viral infections. They restrict viral replication and diffusion through phagocytosis, degranulation, respiratory burst,... (Review)
Review
Neutrophils play multiple roles in acute viral infections. They restrict viral replication and diffusion through phagocytosis, degranulation, respiratory burst, secretion of cytokines, and the release of neutrophil extracellular traps, as well as, activate the adaptive immune response. However, the overactivation of neutrophils may cause tissue damage and lead to poor outcomes. Additionally, some characteristics and functions of neutrophils, such as cell number, lifespan, and antiviral capability, can be influenced while eliminating viruses. This review provides a general description of the protective and pathological roles of neutrophils in acute viral infection.
Topics: Adaptive Immunity; Extracellular Traps; Humans; Neutrophils; Phagocytosis; Virus Diseases
PubMed: 34472718
DOI: 10.1002/iid3.500 -
Nature Communications Nov 2021Lung diseases, such as cystic fibrosis and COPD, are characterized by mucus obstruction and chronic airway inflammation, but their mechanistic link remains poorly...
Lung diseases, such as cystic fibrosis and COPD, are characterized by mucus obstruction and chronic airway inflammation, but their mechanistic link remains poorly understood. Here, we focus on the function of the mucostatic airway microenvironment on epigenetic reprogramming of airway macrophages (AM) and resulting transcriptomic and phenotypical changes. Using a mouse model of muco-obstructive lung disease (Scnn1b-transgenic), we identify epigenetically controlled, differentially regulated pathways and transcription factors involved in inflammatory responses and macrophage polarization. Functionally, AMs from Scnn1b-transgenic mice have reduced efferocytosis and phagocytosis, and excessive inflammatory responses upon lipopolysaccharide challenge, mediated through enhanced Irf1 function and expression. Ex vivo stimulation of wild-type AMs with native mucus impairs efferocytosis and phagocytosis capacities. In addition, mucus induces gene expression changes, comparable with those observed in AMs from Scnn1b-transgenic mice. Our data show that mucostasis induces epigenetic reprogramming of AMs, leading to changes favoring tissue damage and disease progression. Targeting these altered AMs may support therapeutic approaches in patients with muco-obstructive lung diseases.
Topics: Animals; Cystic Fibrosis; Epigenomics; Epithelial Sodium Channels; Female; Flow Cytometry; Humans; Immunohistochemistry; Macrophages, Alveolar; Mice; Phagocytosis; Pulmonary Disease, Chronic Obstructive
PubMed: 34764283
DOI: 10.1038/s41467-021-26777-9 -
Nature Communications May 2023Glial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms...
Glial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms governing the efficiency of debris degradation in glia have remained largely unexplored. Here we show that LC3-associated phagocytosis (LAP), an engulfment pathway assisted by certain autophagy factors, promotes glial phagosome maturation in the Drosophila wing nerve. A LAP-specific subset of autophagy-related genes is required in glia for axon debris clearance, encoding members of the Atg8a (LC3) conjugation system and the Vps34 lipid kinase complex including UVRAG and Rubicon. Phagosomal Rubicon and Atg16 WD40 domain-dependent conjugation of Atg8a mediate proper breakdown of internalized axon fragments, and Rubicon overexpression in glia accelerates debris elimination. Finally, LAP promotes survival following traumatic brain injury. Our results reveal a role of glial LAP in the clearance of neuronal debris in vivo, with potential implications for the recovery of the injured nervous system.
Topics: Animals; Drosophila; Microtubule-Associated Proteins; Phagocytosis; Autophagy; Axons; Neuroglia
PubMed: 37248218
DOI: 10.1038/s41467-023-38755-4 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2022With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing... (Review)
Review
With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing global health crisis. Recent studies have indicated that microglia-neuron interactions are critical for maintaining homeostasis of the central nervous system. Genome-Wide Association Studies and brain imaging studies have suggested that microglia are activated in early stage of neurodegenerative diseases. Microglia are specialized phagocytes in the brain. The discovery of a new phagocytic pathway, trogocytosis, suggests that there is a close interaction between microglia and surviving neurons. In this review, we summarize the important roles of microglia in neurodegenerative diseases, and further analyze the functions and molecular mechanisms of microglia phagocytosis and trogocytosis.
Topics: Alzheimer Disease; Genome-Wide Association Study; Humans; Microglia; Neurodegenerative Diseases; Phagocytosis
PubMed: 35503076
DOI: No ID Found -
Pharmacology & Therapeutics Jan 2022Cell death and the clearance of apoptotic cells are tightly regulated by various signaling molecules in order to maintain physiological tissue function and homeostasis.... (Review)
Review
Cell death and the clearance of apoptotic cells are tightly regulated by various signaling molecules in order to maintain physiological tissue function and homeostasis. The phagocytic removal of apoptotic cells is known as the process of efferocytosis, and abnormal efferocytosis is linked to various health complications and diseases, such as cardiovascular disease, inflammatory diseases, and autoimmune diseases. During efferocytosis, phagocytic cells and/or apoptotic cells release signals, such as "find me" and "eat me" signals, to stimulate the phagocytic engulfment of apoptotic cells. Primary phagocytic cells are macrophages and dendritic cells; however, more recently, other neighboring cell types have also been shown to exhibit phagocytic character, including endothelial cells and fibroblasts, although they are comparatively slower in clearing dead cells. In this review, we focus on macrophage efferocytosis of vascular cells, such as endothelial cells, smooth muscle cells, fibroblasts, and pericytes, and its relation to the progression and development of cardiovascular disease. We also highlight the role of efferocytosis-related molecules and their contribution to the maintenance of vascular homeostasis.
Topics: Apoptosis; Cardiovascular Diseases; Endothelial Cells; Humans; Macrophages; Phagocytosis
PubMed: 34171333
DOI: 10.1016/j.pharmthera.2021.107919 -
Frontiers in Immunology 2022is the most common pathogen causing clinical infections. Neutrophils are a key member of the host innate immunity that plays an essential role in clearing invading .... (Review)
Review
is the most common pathogen causing clinical infections. Neutrophils are a key member of the host innate immunity that plays an essential role in clearing invading . In addition to the well-known defensive approaches such as phagocytosis, degranulation, and reactive oxygen species production, the formation of neutrophil extracellular traps (NETs) has also become an important way for neutrophils to defend against various pathogens. has been reported to be capable of activating neutrophils to release NETs that subsequently kill fungi. The induction of NETs is affected by both the morphology and virulence factors of , which also develops specific strategies to respond to the attack by NETs. Our review specifically focuses on the mechanisms by which triggers NET formation and their subsequent interactions, which might provide meaningful insight into the innate immunity against infection.
Topics: Candida albicans; Candidiasis; Extracellular Traps; Neutrophils; Phagocytosis
PubMed: 35784323
DOI: 10.3389/fimmu.2022.913028 -
International Journal of Molecular... Feb 2023Phagocytosis is one of the most polarised of all cellular activities. Both the stimulus (the target for phagocytosis) and the response (its internalisation) are focussed... (Review)
Review
Phagocytosis is one of the most polarised of all cellular activities. Both the stimulus (the target for phagocytosis) and the response (its internalisation) are focussed at just one part of the cell. At the locus, and this locus alone, pseudopodia form a phagocytic cup around the particle, the cytoskeleton is rearranged, the plasma membrane is reorganised, and a new internal organelle, the phagosome, is formed. The effect of signals from the stimulus must, thus, both be complex and yet be restricted in space and time to enable an effective focussed response. While many aspects of phagocytosis are being uncovered, the mechanism for the restriction of signalling or the effects of signalling remains obscure. In this review, the details of the problem of restricting chemical intracellular signalling are presented, with a focus on diffusion into the cytosol and of signalling lipids along the plasma membrane. The possible ways in which simple diffusion is overcome so that the restriction of signalling and effective phagocytosis can be achieved are discussed in the light of recent advances in imaging, biophysics, and cell biochemistry which together are providing new insights into this area.
Topics: Phagocytosis; Phagosomes; Pseudopodia; Cytoskeleton; Cytosol
PubMed: 36769146
DOI: 10.3390/ijms24032825 -
Immunological Reviews Oct 2023The clearance of dead and dying cells, termed efferocytosis, is a rapid and efficient process and one that is critical for organismal health. The extraordinary speed and... (Review)
Review
The clearance of dead and dying cells, termed efferocytosis, is a rapid and efficient process and one that is critical for organismal health. The extraordinary speed and efficiency with which dead cells are detected and engulfed by immune cells within tissues presents a challenge to researchers who wish to unravel this fascinating process, since these fleeting moments of uptake are almost impossible to catch in vivo. In recent years, the fruit fly (Drosophila melanogaster) embryo has emerged as a powerful model to circumvent this problem. With its abundance of dying cells, specialist phagocytes and relative ease of live imaging, the humble fly embryo provides a unique opportunity to catch and study the moment of cell engulfment in real-time within a living animal. In this review, we explore the recent advances that have come from studies in the fly, and how live imaging and genetics have revealed a previously unappreciated level of diversity in the efferocytic program. A variety of efferocytic strategies across the phagocytic cell population ensure efficient and rapid clearance of corpses wherever death is encountered within the varied and complex setting of a multicellular living organism.
Topics: Animals; Humans; Drosophila melanogaster; Apoptosis; Phagocytosis; Phagocytes; Drosophila
PubMed: 37589239
DOI: 10.1111/imr.13266 -
Current Opinion in Cell Biology Oct 2020Phagocytosis is a widespread and evolutionarily conserved process with diverse biological functions, ranging from engulfment of invading microbes during infection to... (Review)
Review
Phagocytosis is a widespread and evolutionarily conserved process with diverse biological functions, ranging from engulfment of invading microbes during infection to clearance of apoptotic debris in tissue homeostasis. Along with differences in biochemical composition, phagocytic targets greatly differ in physical attributes, such as size, shape, and rigidity, which are now recognized as important regulators of this process. Force exertion at the cell-target interface and cellular mechanical changes during phagocytosis are emerging as crucial factors underlying sensing of such target properties. With technological developments, mechanical aspects of phagocytosis are increasingly accessible experimentally, revealing remarkable organizational complexity of force exertion. An increasingly high-resolution picture is emerging of how target physical cues and cellular mechanical properties jointly govern important steps throughout phagocytic engulfment.
Topics: Animals; Biophysical Phenomena; Mechanotransduction, Cellular; Phagocytes; Phagocytosis
PubMed: 32698097
DOI: 10.1016/j.ceb.2020.05.011