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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 2020The spirochetal bacteria spp. are causative agents of leptospirosis, a globally neglected and reemerging zoonotic disease. Infection with these pathogens may lead to an... (Review)
Review
The spirochetal bacteria spp. are causative agents of leptospirosis, a globally neglected and reemerging zoonotic disease. Infection with these pathogens may lead to an acute and potentially fatal disease but also to chronic asymptomatic renal colonization. Both forms of disease demonstrate the ability of leptospires to evade the immune response of their hosts. In this review, we aim first to recapitulate the knowledge and explore the controversial data about the opsonization, recognition, intracellular survival, and killing of leptospires by scavenger cells, including platelets, neutrophils, macrophages, and dendritic cells. Second, we will summarize the known specificities of the recognition or escape of leptospire components (the so-called microbial-associated molecular patterns; MAMPs) by the pattern recognition receptors (PRRs) of the Toll-like and NOD-like families. These PRRs are expressed by phagocytes, and their stimulation by MAMPs triggers pro-inflammatory cytokine and chemokine production and bactericidal responses, such as antimicrobial peptide secretion and reactive oxygen species production. Finally, we will highlight recent studies suggesting that boosting or restoring phagocytic functions by treatments using agonists of the Toll-like or NOD receptors represents a novel prophylactic strategy and describe other potential therapeutic or vaccine strategies to combat leptospirosis.
Topics: Animals; Humans; Immune Evasion; Immunity, Innate; Leptospira; Leptospirosis; Macrophages; NLR Proteins; Neutrophils; Phagocytes; Phagocytosis; Toll-Like Receptors
PubMed: 33123147
DOI: 10.3389/fimmu.2020.571816 -
Microbiology Spectrum Apr 2016Since the ability of some cells to engulf particulate material was observed before Metchnikoff, he did not "discover" phagocytosis, as is sometimes mentioned in... (Review)
Review
Since the ability of some cells to engulf particulate material was observed before Metchnikoff, he did not "discover" phagocytosis, as is sometimes mentioned in textbooks. Rather, he assigned to particle internalization the role of defending the host against noxious stimuli, which represented a new function relative to the previously recognized task of intracellular digestion. With this proposal, Metchnikoff built the conceptual framework within which immunity could finally be seen as an active host function triggered by noxious stimuli. In this sense, Metchnikoff can be rightly regarded as the father of all immunological sciences and not only of innate immunity or myeloid cell biology. Moreover, the recognition properties of his phagocyte fit surprisingly well with recent discoveries and modern models of immune sensing. For example, rather than assigning to immune recognition exclusively the function of eliminating nonself components (as others did after him), Metchnikoff viewed phagocytes as homeostatic agents capable of monitoring the internal environment and promoting tissue remodeling, thereby continuously defining the identity of the organism. No doubt, Metchnikoff's life and creativity can provide, still today, a rich source of inspiration.
Topics: Allergy and Immunology; History, 19th Century; History, 20th Century; Humans; Immunity, Innate; Myeloid Cells; Phagocytes; Phagocytosis
PubMed: 27227301
DOI: 10.1128/microbiolspec.MCHD-0009-2015 -
International Journal of Medical... Jun 2011The saprophytic fungus Aspergillus fumigatus is a mold which is ubiquitously present in the environment. It produces large numbers of spores, called conidia that we... (Review)
Review
The saprophytic fungus Aspergillus fumigatus is a mold which is ubiquitously present in the environment. It produces large numbers of spores, called conidia that we constantly inhale with the breathing air. Healthy individuals normally do not suffer from true fungal infections with this pathogen. A normally robust resistance against Aspergillus is based on the presence of a very effective immunological defense system in the vertebrate body. Inhaled conidia are first encountered by lung-resident alveolar macrophages and then by neutrophil granulocytes. Both cell types are able to effectively ingest and destroy the fungus. Although some responses of the adaptive immune system develop, the key protection is mediated by innate immunity. The importance of phagocytes for defense against aspergillosis is also supported by large numbers of animal studies. Despite the production of aggressive chemicals that can extracellularly destroy fungal pathogens, the main effector mechanism of the innate immune system is phagocytosis. Very recently, the production of extracellular neutrophil extracellular traps (NETs) consisting of nuclear DNA has been added to the armamentarium that innate immune cells use against infection with Aspergillus. Phagocyte responses to Aspergillus are very broad, and a number of new observations have added to this complexity in recent years. To summarize established and newer findings, we will give an overview on current knowledge of the phagocyte system for the protection against Aspergillus.
Topics: Animals; Aspergillus fumigatus; Humans; Immunity, Innate; Macrophages; Neutrophils; Phagocytes; Phagocytosis
PubMed: 21571589
DOI: 10.1016/j.ijmm.2011.04.012 -
Inflammatory Bowel Diseases Oct 2008Inflammatory bowel diseases are common chronic inflammatory disorders. The majority are idiopathic and can be broadly divided into Crohn's disease and ulcerative... (Review)
Review
Inflammatory bowel diseases are common chronic inflammatory disorders. The majority are idiopathic and can be broadly divided into Crohn's disease and ulcerative colitis. Their cause is unknown, but most hypotheses focus on a primary role for T-cell dysfunction. Conversely, there is a collection of congenital disorders of phagocyte function that result not only in immunodeficiency but also in noninfectious inflammatory bowel disease. In all cases, the latter is strikingly reminiscent of the clinical and pathological features of Crohn's disease. This coincides with recent work demonstrating that despite previous emphasis on adaptive immune dysfunction, patients with Crohn's disease actually possess an unusually weak acute innate inflammatory response. This review consolidates the literature on inflammatory bowel disease in congenital immunodeficiencies and considers the role of phagocyte dysfunction in Crohn's disease. Concepts about pathogenesis and treatment that can be carried across these disorders are also discussed.
Topics: Humans; Immunity, Innate; Inflammatory Bowel Diseases; Neutrophils; Phagocytes; Respiratory Burst
PubMed: 18421761
DOI: 10.1002/ibd.20449 -
Cellular Immunology 2014Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte... (Review)
Review
Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte phagocyte subsets to the damaged heart, the latter of which may give rise briefly to differentiated macrophage-like or dendritic-like cells. Within the injured myocardium, a primary function of these phagocytic cells is to remove damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as immune cells that turn over. Recognition of dying cellular targets by phagocytes triggers intracellular signaling, particularly in macrophages, wherein cytokines and lipid mediators are generated to promote inflammation resolution, fibrotic scarring, angiogenesis, and compensatory organ remodeling. These actions cooperate in an effort to preserve myocardial contractility and prevent heart failure. Immune cell function is modulated by local tissue factors that include secreted protease activity, oxidative stress during clinical reperfusion, and hypoxia. Importantly, experimental evidence suggests that monocyte function and phagocytosis efficiency is compromised in the setting of MI risk factors, including hyperlipidemia and ageing, however underlying mechanisms remain unclear. Herein we review seminal phagocyte and cardiac molecular factors that lead to, and culminate in, the recognition and removal of dying injured myocardium, the effects of hypoxia, and their relationship to cardiac infarct size and heart healing.
Topics: Animals; Cell Hypoxia; Humans; Inflammation; Mice; Myocardial Infarction; Myocytes, Cardiac; Phagocytes; Wound Healing
PubMed: 24862542
DOI: 10.1016/j.cellimm.2014.04.006 -
Annals of Internal Medicine Apr 1980Recent advances in understanding the physiologic and biochemical bases for recruitment of phagocytes to inflammatory sites has led to the recognition of patients who... (Review)
Review
Recent advances in understanding the physiologic and biochemical bases for recruitment of phagocytes to inflammatory sites has led to the recognition of patients who have recurrent infections because of abnormalities of phagocyte chemotaxis. In some of these patients there is abnormal chemoattractant mediator production or regulation, whereas in others there are defects in phagocytic cell function. The cellular defects in chemotaxis can be characterized as either intrinsic defects of the cellular motility apparatus or acquired defects from mediators influencing cell function or from shifts in circulating phagocyte subpopulations. Systematic study of these defects has resulted in functional, biochemical, and ultrastructural characterization of abnormal phagocyte chemotaxis in certain patients, and in some patients study has led to rational approaches for treatment. Clinical trials assessing the efficacy of such pharmacologic agents are underway.
Topics: Adolescent; Adult; Burns; Chemotactic Factors; Chemotaxis; Chemotaxis, Leukocyte; Child; Cytoplasmic Granules; Female; Humans; Immune Adherence Reaction; Immunoglobulin E; Infections; Kartagener Syndrome; Lymphocytes; Male; Neutrophils; Phagocytes; Phagocytosis; Recurrence
PubMed: 6987931
DOI: 10.7326/0003-4819-92-4-520 -
Nature Reviews. Immunology Jun 2010Neutrophils, monocytes and macrophages are closely related phagocytic cells that cooperate during the onset, progression and resolution of inflammation. This Review... (Review)
Review
Neutrophils, monocytes and macrophages are closely related phagocytic cells that cooperate during the onset, progression and resolution of inflammation. This Review highlights the mechanisms involved in the intimate partnership of phagocytes during each progressive phase of the inflammatory response. We describe how tissue-resident macrophages recognize tissue damage to promote the recruitment of neutrophils and the mechanisms by which infiltrating neutrophils can then promote monocyte recruitment. Furthermore, we discuss the phagocyte-derived signals that abrogate neutrophil recruitment and how the uptake of apoptotic neutrophils by macrophages leads to termination of the inflammatory response. Finally, we highlight the potential therapeutic relevance of these interactions.
Topics: Animals; Apoptosis; Cell Movement; Homeostasis; Humans; Inflammation; Phagocytes; Signal Transduction
PubMed: 20498669
DOI: 10.1038/nri2779 -
PLoS Pathogens 2012
Review
Topics: Animals; Humans; Phagocytes; Toxoplasma; Toxoplasmosis
PubMed: 22876173
DOI: 10.1371/journal.ppat.1002794 -
BMC Veterinary Research Jul 2020Emergence of both viral zoonoses from bats and diseases that threaten bat populations has highlighted the necessity for greater insights into the functioning of the bat...
BACKGROUND
Emergence of both viral zoonoses from bats and diseases that threaten bat populations has highlighted the necessity for greater insights into the functioning of the bat immune system. Particularly when considering hibernating temperate bat species, it is important to understand the seasonal dynamics associated with immune response. Body temperature is one of the factors that modulates immune functions and defence mechanisms against pathogenic agents in vertebrates. To better understand innate immunity mediated by phagocytes in bats, we measured respiratory burst and haematology and blood chemistry parameters in heterothermic greater mouse-eared bats (Myotis myotis) and noctules (Nyctalus noctula) and homeothermic laboratory mice (Mus musculus).
RESULTS
Bats displayed similar electrolyte levels and time-related parameters of phagocyte activity, but differed in blood profile parameters related to metabolism and red blood cell count. Greater mouse-eared bats differed from mice in all phagocyte activity parameters and had the lowest phagocytic activity overall, while noctules had the same quantitative phagocytic values as mice. Homeothermic mice were clustered separately in a high phagocyte activity group, while both heterothermic bat species were mixed in two lower phagocyte activity clusters. Stepwise regression identified glucose, white blood cell count, haemoglobin, total dissolved carbon dioxide and chloride variables as the best predictors of phagocyte activity. White blood cell counts, representing phagocyte numbers available for respiratory burst, were the best predictors of both time-related and quantitative parameters of phagocyte activity. Haemoglobin, as a proxy variable for oxygen available for uptake by phagocytes, was important for the onset of phagocytosis.
CONCLUSIONS
Our comparative data indicate that phagocyte activity reflects the physiological state and blood metabolic and cellular characteristics of homeothermic and heterothermic mammals. However, further studies elucidating trade-offs between immune defence, seasonal lifestyle physiology, hibernation behaviour, roosting ecology and geographic patterns of immunity of heterothermic bat species will be necessary. An improved understanding of bat immune responses will have positive ramifications for wildlife and conservation medicine.
Topics: Animals; Behavior, Animal; Blood Chemical Analysis; Body Temperature; Chiroptera; Erythrocyte Count; Phagocytes
PubMed: 32631329
DOI: 10.1186/s12917-020-02450-z