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Pharmacological Research May 2023Nicotinic acetylcholine receptors are not only expressed by the nervous system and at the neuro-muscular junction but also by mononuclear phagocytes, which belong to the... (Review)
Review
Nicotinic acetylcholine receptors are not only expressed by the nervous system and at the neuro-muscular junction but also by mononuclear phagocytes, which belong to the innate immune system. Mononuclear phagocyte is an umbrella term for monocytes, macrophages, and dendritic cells. These cells play pivotal roles in host defense against infection but also in numerous often debilitating diseases that are characterized by exuberant inflammation. Nicotinic acetylcholine receptors of the neuronal type dominate in these cells, and their stimulation is mainly associated with anti-inflammatory effects. Although the cholinergic modulation of mononuclear phagocytes is of eminent clinical relevance for the prevention and treatment of inflammatory diseases and neuropathic pain, we are only beginning to understand the underlying mechanisms on the molecular level. The purpose of this review is to report and critically discuss the current knowledge on signal transduction mechanisms elicited by nicotinic acetylcholine receptors in mononuclear phagocytes.
Topics: Humans; Receptors, Nicotinic; Macrophages; Monocytes; Signal Transduction; Inflammation
PubMed: 36966897
DOI: 10.1016/j.phrs.2023.106727 -
Trends in Parasitology Nov 2022The opportunistic protist Acanthamoeba, which interacts with other microbes such as bacteria, fungi, and viruses, shows significant similarity in cellular and functional... (Review)
Review
The opportunistic protist Acanthamoeba, which interacts with other microbes such as bacteria, fungi, and viruses, shows significant similarity in cellular and functional aspects to human macrophages. Intracellular survival of microbes in this microbivorous amoebal host may be a crucial step for initiation of infection in higher eukaryotic cells. Therefore, Acanthamoeba-microbe adaptations are considered an evolutionary model of macrophage-pathogen interactions. This paper reviews Acanthamoeba as an emerging human pathogen and different ecological interactions between Acanthamoeba and microbes that may serve as environmental training grounds and a genetic melting pot for the evolution, persistence, and transmission of potential human pathogens.
Topics: Acanthamoeba; Bacteria; Fungi; Humans; Macrophages; Phagocytes
PubMed: 36109313
DOI: 10.1016/j.pt.2022.08.007 -
Current Opinion in Immunology Oct 2019The innate immune system has evolved to recognize diverse microbes and destroy them. At the same time, microbial pathogens undermine immunity to cause disease. Here, we... (Review)
Review
The innate immune system has evolved to recognize diverse microbes and destroy them. At the same time, microbial pathogens undermine immunity to cause disease. Here, we highlight recent advances in understanding an antimicrobial pathway called LC3-associated phagocytosis (LAP), which combines features of autophagy with phagocytosis. Upon phagocytosis, many microbes, including bacteria, fungi, and parasites, are sequestered in an LC3-positive, single-membrane bound compartment, a hallmark of LAP. LAP depends upon NADPH oxidase activity at the incipient phagosome and culminates in lysosomal trafficking and microbial degradation. Most often LAP is an effective host defense, but some pathogens evade LAP or replicate successfully in this microenvironment. Here, we review how LAP targets microbial pathogens and strategies pathogens employ to circumvent LAP.
Topics: Animals; Biomarkers; Host-Pathogen Interactions; Humans; Immunity, Innate; Macroautophagy; Microtubule-Associated Proteins; Oxidation-Reduction; Phagocytes; Phagocytosis; Phagosomes; Signal Transduction
PubMed: 31247378
DOI: 10.1016/j.coi.2019.04.012 -
Immunological Reviews Mar 2024Since their description by Metchnikoff in 1905, phagocytes have been increasingly recognized to be the entities that traffic to sites of infection and inflammation,... (Review)
Review
Since their description by Metchnikoff in 1905, phagocytes have been increasingly recognized to be the entities that traffic to sites of infection and inflammation, engulf and kill infecting organisms, and clear out apoptotic debris all the while making antigens available and accessible to the lymphoid organs for future use. Therefore, phagocytes provide the gateway and the first check in host protection and immune response. Disorders in killing and chemotaxis lead not only to infection susceptibility, but also to autoimmunity. We aim to describe chronic granulomatous disease and the leukocyte adhesion deficiencies as well as myeloperoxidase deficiency and G6PD deficiency as paradigms of critical pathways.
Topics: Humans; Neutrophils; Granulomatous Disease, Chronic; Phagocytosis; Phagocytes; Inflammation
PubMed: 38429865
DOI: 10.1111/imr.13308 -
British Journal of Pharmacology May 2024Human neutrophils are components of the innate immune system and are the most abundant white blood cells in the circulation. They are professional phagocytes and express... (Review)
Review
Human neutrophils are components of the innate immune system and are the most abundant white blood cells in the circulation. They are professional phagocytes and express several G protein-coupled receptors (GPCRs), which are essential for proper neutrophil functions. So far, the two formyl peptide receptors, FPR1 and FPR2, have been the most extensively studied group of neutrophil GPCRs, but recently, a new group, the free fatty acid (FFA) receptors, has attracted growing attention. Neutrophils express two FFA receptors, GPR84 and FFA2, which sense medium- and short-chain fatty acids respectively, and display similar activation profiles. The exact pathophysiological role of GPR84 is not yet fully understood, but it is generally regarded as a pro-inflammatory receptor that mediates neutrophil activation. In this review, we summarize current knowledge of how GPR84 affects human neutrophil functions and discuss the regulatory mechanisms that control these responses, focusing on the similarities and differences in comparison to the two FPRs and FFA2. LINKED ARTICLES: This article is part of a themed issue GPR84 Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc.
Topics: Humans; Neutrophils; Signal Transduction; Receptors, Formyl Peptide; Phagocytes; Receptors, G-Protein-Coupled
PubMed: 36869866
DOI: 10.1111/bph.16066 -
Frontiers in Immunology 2021Phagocytes, which include neutrophils, monocytes, macrophages, and dendritic cells, protect the body by removing foreign particles, bacteria, and dead or dying cells.... (Review)
Review
Phagocytes, which include neutrophils, monocytes, macrophages, and dendritic cells, protect the body by removing foreign particles, bacteria, and dead or dying cells. Phagocytic integrins are greatly involved in the recognition of and adhesion to specific antigens on cells and pathogens during phagocytosis as well as the recruitment of immune cells. β2 integrins, including αLβ2, αMβ2, αXβ2, and αDβ2, are the major integrins presented on the phagocyte surface. The activation of β2 integrins is essential to the recruitment and phagocytic function of these phagocytes and is critical for the regulation of inflammation and immune defense. However, aberrant activation of β2 integrins aggravates auto-immune diseases, such as psoriasis, arthritis, and multiple sclerosis, and facilitates tumor metastasis, making them double-edged swords as candidates for therapeutic intervention. Therefore, precise regulation of phagocyte activities by targeting β2 integrins should promote their host defense functions with minimal side effects on other cells. Here, we reviewed advances in the regulatory mechanisms underlying β2 integrin inside-out signaling, as well as the roles of β2 integrin activation in phagocyte functions.
Topics: Animals; CD18 Antigens; Humans; Phagocytes; Phagocytosis; Signal Transduction
PubMed: 33868253
DOI: 10.3389/fimmu.2021.633639 -
Small (Weinheim An Der Bergstrasse,... Aug 2019Incapability of effective cross-talk with biological environments has partly impaired the in vivo functionality of nanoparticles (NPs). Homing, biodistribution, and... (Review)
Review
Incapability of effective cross-talk with biological environments has partly impaired the in vivo functionality of nanoparticles (NPs). Homing, biodistribution, and function of NPs could be engineered through regulating their interactions with in vivo niches. Inspired by communications in biological systems, endowing a "biological identity" to synthetic NPs is one approach to control their biodistribution, and immunonegotiation profiles. This synthetic-biological combination is referred to as biohybrid NPs, which comprise both i) engineerable, readily producible, and trackable synthetic NPs as well as ii) biological moieties with the capability to cross-talk with immunological barriers. Here, the latest understanding on the in vivo interactions of NPs, biological barriers they face, and emerging methods for quantitative measurements of NPs' biodistribution are reviewed. Some key biomolecules that have emerged as negotiators with the immune system in the context of cancer and autoimmunity, and their inspirations on biohybrid NPs are introduced. Critical design considerations for efficient cross-talk between NPs and innate and adaptive immunity followed by hybridization methods are also discussed. Finally, clinical translation challenges and future perspectives regarding biohybrid NPs are discussed.
Topics: Animals; Gene Transfer Techniques; Humans; Immunity; Nanoparticles; Phagocytes; Precision Medicine; Tissue Distribution
PubMed: 31250985
DOI: 10.1002/smll.201902333 -
ELife Nov 2022Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce...
Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions that participate in pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the physiological importance of this complex, its structure remains elusive. Here, we reported the cryo-EM structure of the functional human NOX2-p22 complex in nanodisc in the resting state. NOX2 shows a canonical 6-TM architecture of NOX and p22 has four transmembrane helices. M3, M4, and M5 of NOX2, and M1 and M4 helices of p22 are involved in the heterodimer formation. Dehydrogenase (DH) domain of NOX2 in the resting state is not optimally docked onto the transmembrane domain, leading to inefficient electron transfer and NADPH binding. Structural analysis suggests that the cytosolic factors might activate the NOX2-p22 complex by stabilizing the DH in a productive docked conformation.
Topics: Humans; NADPH Oxidases; NADP; Phagocytes; Superoxides; Membrane Proteins
PubMed: 36413210
DOI: 10.7554/eLife.83743 -
Methods in Molecular Biology (Clifton,... 2023Phagocytosis is carried out by cells such as macrophages of the immune system, whereby particulates like bacteria and apoptotic bodies are engulfed and sequestered...
Phagocytosis is carried out by cells such as macrophages of the immune system, whereby particulates like bacteria and apoptotic bodies are engulfed and sequestered within phagosomes for subsequent degradation. Hence, phagocytosis is important for infection resolution and tissue homeostasis. Aided by the innate and adaptive immune system, the activation of various phagocytic receptors triggers a cascade of downstream signaling mediators that drive actin and plasma membrane remodeling to entrap the bound particulate within the phagosome. Modulation of these molecular players can lead to distinct changes in the capacity and rates of phagocytosis. Here, we present a fluorescence microscopy-based technique to quantify phagocytosis using a macrophage-like cell line. We exemplify the technique through the phagocytosis of antibody-opsonized polystyrene beads and Escherichia coli. This method can be extended to other phagocytes and phagocytic particles.
Topics: Phagocytosis; Macrophages; Phagosomes; Microscopy, Fluorescence; Fluorescent Antibody Technique
PubMed: 37365459
DOI: 10.1007/978-1-0716-3338-0_3 -
American Journal of Reproductive... Aug 2019Efferocytosis, which is known as the phagocytic clearance of dying cells by professional as well as non-professional phagocytes, including a great number of... (Review)
Review
Efferocytosis, which is known as the phagocytic clearance of dying cells by professional as well as non-professional phagocytes, including a great number of intracellular/extracellular factors and signals, is interrelated with the immune system, contributing to local and systemic homeostasis, especially in tissues with high constitutive rates of apoptosis. Accumulating studies have indicated that immune dysregulation is associated with the pathogenesis of the female reproductive system, which causes preeclampsia (PE), recurrent spontaneous abortion (RSA), ruptured ectopic pregnancy, and so on. And some studies have revealed the pleiotropic and essential role of efferocytosis in these obstetrical disorders. More specifically, the occurrence and development of these diseases were in connection with some efferocytosis-related factors and signals, such as C1q, MBL, and IL-33/ST2. In this review, we systematically review the diverse impacts of efferocytosis in immune system and discuss its relevance to normal and pathological pregnancy. These findings may instruct future basic researches as well as clinical applications of efferocytosis-related factors and signals as latent predictors or therapeutic targets on the obstetrical disorders.
Topics: Abortion, Habitual; Animals; Apoptosis; Female; Humans; Interleukin-33; Macrophages; Mannose-Binding Protein-Associated Serine Proteases; Membrane Glycoproteins; Phagocytes; Phagocytosis; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy, Ectopic; Receptors, Complement
PubMed: 30614132
DOI: 10.1111/aji.13088