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Microbiology Spectrum Jan 2017The intestine is the tissue of the body with the highest constitutive exposure to foreign antigen and is also a common entry portal for many local and systemic... (Review)
Review
The intestine is the tissue of the body with the highest constitutive exposure to foreign antigen and is also a common entry portal for many local and systemic pathogens. Therefore, the local immune system has the unenviable task of balancing efficient responses to dangerous pathogens with tolerance toward beneficial microbiota and food antigens. As in most tissues, the decision between tolerance and immunity is critically governed by the activity of local myeloid cells. However, the unique challenges posed by the intestinal environment have necessitated the development of several specialized mononuclear phagocyte populations with distinct phenotypic and functional characteristics that have vital roles in maintaining barrier function and immune homeostasis in the intestine. Intestinal mononuclear phagocyte populations, comprising dendritic cells and macrophages, are crucial for raising appropriate active immune responses against ingested pathogens. Recent technical advances, including microsurgical approaches allowing collection of cells migrating in intestinal lymph, intravital microscopy, and novel gene-targeting approaches, have led to clearer distinctions between mononuclear phagocyte populations in intestinal tissue. In this review, we present an overview of the various subpopulations of intestinal mononuclear phagocytes and discuss their phenotypic and functional characteristics. We also outline their roles in host protection from infection and their regulatory functions in maintaining immune tolerance toward beneficial intestinal antigens.
Topics: Animals; Humans; Immune Tolerance; Immunity, Innate; Intestinal Diseases; Intestines; Leukocytes, Mononuclear; Phagocytes
PubMed: 28102120
DOI: 10.1128/microbiolspec.MCHD-0047-2016 -
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 -
Mucosal Immunology Jul 2017The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and... (Review)
Review
The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt to deal with the challenges specific to their environment. Understanding these processes should help target individual subsets for 'fine tuning' immunological responses within the intestine, a process that may be of relevance both for the treatment of inflammatory bowel disease (IBD) and for optimized vaccine design.
Topics: Animals; Humans; Immunity, Mucosal; Immunomodulation; Immunotherapy; Inflammatory Bowel Diseases; Intestinal Mucosa; Leukocytes, Mononuclear; Phagocytes; Vaccines
PubMed: 28378807
DOI: 10.1038/mi.2017.22 -
Trends in Cell Biology Apr 2018Specialized phagocytes are a newly appreciated classification of phagocyte that currently encompasses Sertoli cells (SCs) of the testes and the retinal pigment... (Review)
Review
Specialized phagocytes are a newly appreciated classification of phagocyte that currently encompasses Sertoli cells (SCs) of the testes and the retinal pigment epithelial cells (RPE) of the retina. While these cells support very different tissues, they have a striking degree of similarity both as phagocytes and in ways that go beyond cell clearance. The clearance of apoptotic germ cells, cell debris, and used photoreceptor outer segments are critical functions of these cells, and the unique nature of their clearance events make specialized phagocytes uniquely suited for studying the larger implications of cell clearance in vivo. The shared functions of specialized phagocytes could provide novel insights into how phagocytosis impacts tissue homeostasis and immune modulation. In this review, we examine the remarkable similarities between SCs and RPE as specialized phagocytes and the physiological effects of cell clearance within a tissue.
Topics: Animals; Homeostasis; Humans; Male; Phagocytes; Phagocytosis; Retina; Retinal Pigment Epithelium; Sertoli Cells; Testis
PubMed: 29454661
DOI: 10.1016/j.tcb.2018.01.004 -
Cold Spring Harbor Perspectives in... Apr 2020Multicellular organisms are not created through cell proliferation alone. It is through cell death that an indefinite cellular mass is pared back to reveal its true... (Review)
Review
Multicellular organisms are not created through cell proliferation alone. It is through cell death that an indefinite cellular mass is pared back to reveal its true form. Cells are also lost throughout life as part of homeostasis and through injury. This detritus represents a significant burden to the living organism and must be cleared, most notably through the use of specialized phagocytic cells. Our understanding of these phagocytes and how they engulf cell corpses has been greatly aided by studying the fruit fly, Here we review the contribution of research to our understanding of how phagocytes respond to cell death. We focus on the best studied phagocytes in the fly: the glia of the central nervous system, the ovarian follicle cells, and the macrophage-like hemocytes. Each is explored in the context of the tissue they maintain as well as how they function during development and in response to injury.
Topics: Animals; Apoptosis; Astrocytes; Cell Death; Cell Proliferation; Central Nervous System; Drosophila Proteins; Drosophila melanogaster; Female; Hemocytes; Homeostasis; Inflammation; Macrophages; Neuroglia; Ovarian Follicle; Phagocytes; Phagocytosis
PubMed: 31501193
DOI: 10.1101/cshperspect.a036350 -
Current Opinion in Microbiology Dec 2017Mammalian body temperature triggers differentiation of the fungal pathogen Histoplasma capsulatum into yeast cells. The Drk1 regulatory kinase and an interdependent... (Review)
Review
Mammalian body temperature triggers differentiation of the fungal pathogen Histoplasma capsulatum into yeast cells. The Drk1 regulatory kinase and an interdependent network of Ryp transcription factors establish the yeast state. Beyond morphology, the differentiation-dependent expression program equips yeasts for invasion and survival within phagosomes. Yeast cells produce α-glucan and the Eng1 endoglucanase which hide yeasts from immune detection. Secretion of yeast phase-specific Sod3 and CatB detoxify phagocyte-derived reactive oxygen molecules. Histoplasma cells adapt to iron and zinc limitation in activated macrophages by production of siderophores and the Zrt2 transporter, respectively. Yeasts also respond to inflammation-associated hypoxia. Histoplasma pathogenicity thus relies on factors controlled by yeast differentiation as well as environment-dependent responses.
Topics: Animals; Fungal Proteins; Histoplasma; Histoplasmosis; Humans; Phagocytes
PubMed: 29096192
DOI: 10.1016/j.mib.2017.10.003 -
Frontiers in Immunology 2021Phagocytosis is the cellular defense mechanism used to eliminate antigens derived from dysregulated or damaged cells, and microbial pathogens. Phagocytosis is therefore...
Phagocytosis is the cellular defense mechanism used to eliminate antigens derived from dysregulated or damaged cells, and microbial pathogens. Phagocytosis is therefore a pillar of innate immunity, whereby foreign particles are engulfed and degraded in lysolitic vesicles. In hexacorallians, phagocytic mechanisms are poorly understood, though putative anthozoan phagocytic cells (amoebocytes) have been identified histologically. We identify and characterize phagocytes from the coral and the sea anemone . Using fluorescence-activated cell sorting and microscopy, we show that distinct populations of phagocytic cells engulf bacteria, fungal antigens, and beads. In addition to pathogenic antigens, we show that phagocytic cells engulf self, damaged cells. We show that target antigens localize to low pH phagolysosomes, and that degradation is occurring within them. Inhibiting actin filament rearrangement interferes with efficient particle phagocytosis but does not affect small molecule pinocytosis. We also demonstrate that cellular markers for lysolitic vesicles and reactive oxygen species (ROS) correlate with hexacorallian phagocytes. These results establish a foundation for improving our understanding of hexacorallian immune cell biology.
Topics: Animals; Anthozoa; Biomarkers; Cytokines; Cytoplasmic Vesicles; Flow Cytometry; Hydrogen-Ion Concentration; Immunity, Innate; Phagocytes; Phagocytosis; Phagosomes; Sea Anemones
PubMed: 34381444
DOI: 10.3389/fimmu.2021.662803 -
The FEBS Journal Feb 2018Phagocytes, such as tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs), are abundant in the stroma of experimental and human tumors and are... (Review)
Review
Phagocytes, such as tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs), are abundant in the stroma of experimental and human tumors and are locally educated to mediate important biological functions that profoundly affect tumor initiation, growth, and dissemination. Of considerable importance is the noncellular component of the tumor microenvironment, namely-the extracellular matrix (ECM). This milieu is often overlooked due to its complexity and vast heterogeneity. Biophysical and biomechanical cues provided by the dynamically evolving tumorigenic ECM fundamentally modulate every behavioral facet of the cancer cells and of associated stromal cells. In this review, we discuss the intricate interplay between phagocytes and ECM that are lined up to support tumor progression. TAMs and TANs shape the tumorigenic ECM by providing key matrix-remodeling enzymes and structural proteins and in turn, the altered tumor ECM modulates their migration and function. A better mechanistic comprehension of this reciprocal dependence has exciting implications for the development of new therapeutic options for cancer.
Topics: Antineoplastic Agents; Extracellular Matrix; Humans; Neoplasms; Phagocytes; Tumor Microenvironment
PubMed: 29106767
DOI: 10.1111/febs.14317 -
Frontiers in Immunology 2020
Topics: Animals; Phagocytes
PubMed: 33362804
DOI: 10.3389/fimmu.2020.628847 -
Current Topics in Microbiology and... 2017During development, stress, infection, or normal homeostasis, billions of cells die on a daily basis, and the responsibility of clearing these cellular corpses lies with... (Review)
Review
During development, stress, infection, or normal homeostasis, billions of cells die on a daily basis, and the responsibility of clearing these cellular corpses lies with the phagocytes of innate immune system. This process, termed efferocytosis , is critical for the prevention of inflammation and autoimmunity , as well as modulation of the adaptive immune response. Defective clearance of dead cells is characteristic of many human autoimmune or autoinflammatory disorders, such as systemic lupus erythematosus (SLE), atherosclerosis, and diabetes. The mechanisms that phagocytes employ to sense, engulf, and process dead cells for an appropriate immune response have been an area of great interest. However, insight into novel mechanisms of programmed cell death , such as necroptosis, has shed light on the fact that while the diner (or phagocyte) is important, the meal itself (the type of dead cell) can play a crucial role in shaping the pursuant immune response.
Topics: Adaptive Immunity; Apoptosis; Autoimmunity; Humans; Immunity, Innate; Inflammation; Phagocytes; Phagocytosis
PubMed: 26305046
DOI: 10.1007/82_2015_467