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Molecular Immunology Mar 2021Alzheimer's disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary...
Alzheimer's disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated in basic microglia function including, phagocytosis, apoptosis, and the inflammatory response to Aβ in mouse brain and primary cells. These studies show that microglia are key players in the response to Aβ and in the accumulation of AD pathology. However, details are still missing about which apoptotic or inflammatory factors rely on TREM2 in their response to Aβ, especially in human cell lines. Given these previous findings our hypothesis is that TREM2 influences the response to Aβ toxicity by enhancing phagocytosis and inhibiting both the BCL-2 family of apoptotic proteins and pro-inflammatory cytokines. Aβ treatment of the human microglial cell line, HMC3 cells, was performed and TREM2 was overexpressed or silenced and the phagocytosis, apoptosis and inflammatory response were evaluated. Results indicate that a robust phagocytic response to Aβ after 24 h requires TREM2 in HMC3 cells. Also, TREM2 inhibits Aβ induced apoptosis by activating the Mcl-1/Bim complex. TREM2 is involved in activation of IP-10, MIP-1a, and IL-8, while it inhibits FGF-2, VEGF and GRO. Taken together, TREM2 plays a role in enhancing the microglial functional response to Aβ toxicity in HMC3 cells. This novel information suggests that therapeutic strategies that seek to activate TREM2 may not only enhance phagocytosis and inhibit apoptosis, but may also inhibit beneficial inflammatory factors, emphasizing the need to define TREM2-related inflammatory activity in not only mouse models of AD, but also in human AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Apoptosis; Brain; Cell Line; Cell Line, Tumor; Hep G2 Cells; Humans; Inflammation; Membrane Glycoproteins; Microglia; Phagocytes; Phagocytosis; Plaque, Amyloid; Receptors, Immunologic; THP-1 Cells; U937 Cells
PubMed: 33461764
DOI: 10.1016/j.molimm.2020.12.035 -
International Journal of Molecular... Oct 2023Cells are the smallest units that make up living organisms, which constantly undergo the processes of proliferation, differentiation, senescence and death. Dead cells... (Review)
Review
Cells are the smallest units that make up living organisms, which constantly undergo the processes of proliferation, differentiation, senescence and death. Dead cells need to be removed in time to maintain the homeostasis of the organism and keep it healthy. This process is called efferocytosis. If the process fails, this may cause different types of diseases. More and more evidence suggests that a faulty efferocytosis process is closely related to the pathological processes of respiratory diseases. In this review, we will first introduce the process and the related mechanisms of efferocytosis of the macrophage. Secondly, we will propose some methods that can regulate the function of efferocytosis at different stages of the process. Next, we will discuss the role of efferocytosis in different lung diseases and the related treatment approaches. Finally, we will summarize the drugs that have been applied in clinical practice that can act upon efferocytosis, in order to provide new ideas for the treatment of lung diseases.
Topics: Humans; Apoptosis; Phagocytosis; Macrophages; Phagocytes; Lung Diseases; Respiration Disorders
PubMed: 37834319
DOI: 10.3390/ijms241914871 -
Frontiers in Immunology 2021The resolution of inflammation is a tissue protective program that is governed by several factors including specialized pro-resolving mediators (SPMs), proteins, gasses... (Review)
Review
The resolution of inflammation is a tissue protective program that is governed by several factors including specialized pro-resolving mediators (SPMs), proteins, gasses and nucleotides. Pro-resolving mediators activate counterregulatory programs to quell inflammation and promote tissue repair in a manner that does not compromise host defense. Phagocytes like neutrophils and macrophages play key roles in the resolution of inflammation because of their ability to remove debris, microbes and dead cells through processes including phagocytosis and efferocytosis. Emerging evidence suggests that failed resolution of inflammation and defective phagocytosis or efferocytosis underpins several prevalent human diseases. Therefore, understanding factors and mechanisms associated with enhancing these processes is a critical need. SPMs enhance phagocytosis and efferocytosis and this review will highlight mechanisms associated with their actions.
Topics: Animals; Cytokines; Humans; Inflammation; Ligands; Macrophages; Mice; Neutrophils; Phagocytes; Phagocytosis
PubMed: 34177900
DOI: 10.3389/fimmu.2021.660865 -
Cell Reports Jul 2023Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient,...
Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient, and cells rapidly die, suggesting the absence of necessary factor(s). KSHV epidemiology unexpectedly mirrors that of malaria and certain helminthic infections, while other herpesviruses are ubiquitous. Elevated circulating monocytes are common in these parasitic infections. Here, we show that KSHV infection of monocytes or M-CSF-differentiated (M2) macrophages is highly efficient. Proteomic analyses demonstrate that infection induces macrophage production of B cell chemoattractants and activating factor. We find that KSHV acts with monocytes or M2 macrophages to stimulate B cell survival, proliferation, and plasmablast differentiation. Further, macrophages drive infected plasma cell differentiation and long-term viral latency. In Kenya, where KSHV is endemic, we find elevated monocyte levels in children with malaria. These findings demonstrate a role for mononuclear phagocytes in KSHV B cell latency and suggest that mononuclear phagocyte abundance may underlie KSHV's geographic disparity.
Topics: Child; Humans; Herpesvirus 8, Human; Proteomics; B-Lymphocytes; Macrophages; Monocytes; Virus Latency
PubMed: 37440412
DOI: 10.1016/j.celrep.2023.112767 -
Infection and Immunity May 2023Brucella spp. are facultatively intracellular bacteria that can infect, survive, and multiply in various host cell types and/or . The genus Brucella has markedly... (Review)
Review
Brucella spp. are facultatively intracellular bacteria that can infect, survive, and multiply in various host cell types and/or . The genus Brucella has markedly expanded in recent years with the identification of novel species and hosts, which has revealed additional information about the cell and tissue tropism of these pathogens. Classically, Brucella spp. are considered to have tropism for organs that contain large populations of phagocytes such as lymph nodes, spleen, and liver, as well as for organs of the genital system, including the uterus, epididymis, testis, and placenta. However, experimental infections of several different cultured cell types indicate that Brucella may actually have a broader cell tropism than previously thought. Indeed, recent studies indicate that certain Brucella species in particular hosts may display a pantropic distribution . This review discusses the available knowledge on cell and tissue tropism of Brucella spp. in natural infections of various host species, as well as in experimental animal models and cultured cells.
Topics: Animals; Male; Female; Brucella; Phagocytes; Cell Line; Cells, Cultured; Tropism; Brucellosis
PubMed: 37129522
DOI: 10.1128/iai.00062-23 -
Current Opinion in Immunology Oct 2019Transition metal ions are essential to bacterial pathogens and their hosts alike but are harmful in excess. In an effort to curtail the replication of intracellular... (Review)
Review
Transition metal ions are essential to bacterial pathogens and their hosts alike but are harmful in excess. In an effort to curtail the replication of intracellular bacteria, host phagocytes exploit both the essentiality and toxicity of transition metals. In the paradigmatic description of nutritional immunity, iron and manganese are withheld from phagosomes to starve microbial invaders of these nutrients. Conversely, the destructive properties of copper and zinc appear to be harnessed by phagocytes, where these metals are delivered in excess to phagosomes to intoxicate internalized bacteria. Here, we briefly summarize key players in metal withholding from intracellular pathogens, before focusing on recent findings supporting the function of copper and zinc as phagocyte antimicrobial effectors. The mechanisms of copper and zinc toxicity are explored, along with strategies employed by intracellular bacterial pathogens to avoid killing by these metals.
Topics: Anti-Bacterial Agents; Bacteria; Copper; Phagocytes; Zinc
PubMed: 31063946
DOI: 10.1016/j.coi.2019.04.002 -
International Journal of Biological... Apr 2022Phagocytosis is a cellular process maintaining tissue balance and plays an essential role in initiating the innate immune response. The process of phagocytosis was... (Review)
Review
Phagocytosis is a cellular process maintaining tissue balance and plays an essential role in initiating the innate immune response. The process of phagocytosis was triggered by the binding of pathogen-associated molecular patterns (PAMP) with their cell surface receptors on the phagocytes. These receptors not only perform phagocytic functions, but also bridge the gap between extracellular and intracellular communication, leading to signal transduction and the production of inflammatory mediators, which are crucial for clearing the invading pathogens and maintaining cell homeostasis. For the past few years, the application of β-glucan comes down to immunoregulation and anti-tumor territory. As a well-known PAMP, β-glucan is one of the most abundant polysaccharides in nature. By binding to specific receptors on immune cells and activating intracellular signal transduction pathways, it causes phagocytosis and promotes the release of cytokines. Further retrieval and straightening out literature related to β-glucan phagocytic receptors will help better elucidate their immunomodulatory functions. This review attempts to summarize physicochemical properties and specific processes involved in β-glucan induced phagocytosis, its phagocytic receptors, and cascade events triggered by β-glucan at the cellular and molecular levels.
Topics: Immunity, Innate; Macrophages; Phagocytes; Phagocytosis; beta-Glucans
PubMed: 35202631
DOI: 10.1016/j.ijbiomac.2022.02.111 -
Frontiers in Immunology 2020Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and... (Review)
Review
Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and environmental particles, as well as remove self-apoptotic cells/cell debris to maintain tissue homeostasis. In crustacean, phagocytosis by hemocyte has also been well-recognized as a crucial defense mechanism for the host against infectious agents such as bacteria and viruses. In this review, we summarized the current knowledge of hemocyte-mediated phagocytosis, in particular focusing on the related receptors for recognition and internalization of pathogens as well as the downstream signal pathways and intracellular regulators involved in the process of hemocyte phagocytosis. We attempted to gain a deeper understanding of the phagocytic mechanism of different hemocytes and their contribution to the host defense immunity in crustaceans.
Topics: Animals; Cell Adhesion Molecules; Crustacea; Hemocytes; Host-Pathogen Interactions; Immunity, Innate; Lectins; Opsonin Proteins; Phagocytes; Phagocytosis; Phagosomes; Pore Forming Cytotoxic Proteins; Receptors, Pattern Recognition; Receptors, Scavenger; Signal Transduction
PubMed: 32194551
DOI: 10.3389/fimmu.2020.00268 -
Neuron Nov 2022CNS-resident macrophages-including parenchymal microglia and border-associated macrophages (BAMs)-contribute to neuronal development and health, vascularization, and... (Review)
Review
CNS-resident macrophages-including parenchymal microglia and border-associated macrophages (BAMs)-contribute to neuronal development and health, vascularization, and tissue integrity at steady state. Border-patrolling mononuclear phagocytes such as dendritic cells and monocytes confer important immune functions to the CNS, protecting it from pathogenic threats including aberrant cell growth and brain malignancies. Even though we have learned much about the contribution of lymphocytes to CNS pathologies, a better understanding of differential roles of tissue-resident and -invading phagocytes is slowly emerging. In this perspective, we propose that in CNS neuroinflammatory diseases, tissue-resident macrophages (TRMs) contribute to the clearing of debris and resolution of inflammation, whereas blood-borne phagocytes are drivers of immunopathology. We discuss the remaining challenges to resolve which specialized mononuclear phagocyte populations are driving or suppressing immune effector function, thereby potentially dictating the outcome of autoimmunity or brain cancer.
Topics: Humans; Mononuclear Phagocyte System; Microglia; Phagocytes; Macrophages; Monocytes; Brain Neoplasms
PubMed: 36327896
DOI: 10.1016/j.neuron.2022.10.005 -
Frontiers in Immunology 2021Following phagocytosis, the nascent phagosome undergoes maturation to become a phagolysosome with an acidic, hydrolytic, and often oxidative lumen that can efficiently... (Review)
Review
Following phagocytosis, the nascent phagosome undergoes maturation to become a phagolysosome with an acidic, hydrolytic, and often oxidative lumen that can efficiently kill and digest engulfed microbes, cells, and debris. The fusion of phagosomes with lysosomes is a principal driver of phagosomal maturation and is targeted by several adapted intracellular pathogens. Impairment of this process has significant consequences for microbial infection, tissue inflammation, the onset of adaptive immunity, and disease. Given the importance of phagosome-lysosome fusion to phagocyte function and the many virulence factors that target it, it is unsurprising that multiple molecular pathways have evolved to mediate this essential process. While the full range of these pathways has yet to be fully characterized, several pathways involving proteins such as members of the Rab GTPases, tethering factors and SNAREs have been identified. Here, we summarize the current state of knowledge to clarify the ambiguities in the field and construct a more comprehensive phagolysosome formation model. Lastly, we discuss how other cellular pathways help support phagolysosome biogenesis and, consequently, phagocyte function.
Topics: Animals; Autophagy; Humans; Lysosomes; Membrane Fusion; Phagocytes; Phagocytosis; Phagosomes; SNARE Proteins; rab GTP-Binding Proteins
PubMed: 33717183
DOI: 10.3389/fimmu.2021.636078