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International Journal of Molecular... Dec 2022The mononuclear phagocytic system (MPS) is the primary innate immune cell group in male reproductive tissues, maintaining the balance of pro-inflammatory and immune... (Review)
Review
The mononuclear phagocytic system (MPS) is the primary innate immune cell group in male reproductive tissues, maintaining the balance of pro-inflammatory and immune tolerance. This article aims to outline the role of mononuclear macrophages in the immune balance of the testes and epididymis, and to understand the inner immune regulation mechanism. A review of pertinent publications was performed using the PubMed and Google Scholar databases on all articles published prior to January 2021. Search terms were based on the following keywords: 'MPS', 'mononuclear phagocytes', 'testes', 'epididymis', 'macrophage', 'Mφ', 'dendritic cell', 'DC', 'TLR', 'immune', 'inflammation', and 'polarization'. Additionally, reference lists of primary and review articles were reviewed for other publications of relevance. This review concluded that MPS exhibits a precise balance in the male reproductive system. In the testes, MPS cells are mainly suppressed subtypes (M2 and cDC2) under physiological conditions, which maintain the local immune tolerance. Under pathological conditions, MPS cells will transform into M1 and cDC1, producing various cytokines, and will activate T cell specific immunity as defense to foreign pathogens or self-antigens. In the epididymis, MPS cells vary in the different segments, which express immune tolerance in the caput and pro-inflammatory condition in the cauda. Collectively, MPS is the control point for maintaining the immune tolerance of the testes and epididymis as well as for eliminating pathogens.
Topics: Male; Humans; Macrophages; Mononuclear Phagocyte System; Epididymis; Testis; T-Lymphocytes
PubMed: 36613494
DOI: 10.3390/ijms24010053 -
Brain Pathology (Zurich, Switzerland) Mar 2023Ischemic stroke (IS) is a major cause of disability and death in adults, and the immune response plays an indispensable role in its pathological process. After the onset... (Review)
Review
Ischemic stroke (IS) is a major cause of disability and death in adults, and the immune response plays an indispensable role in its pathological process. After the onset of IS, an inflammatory storm, with the infiltration and mobilization of the mononuclear phagocyte system (MPS), is triggered in the brain. Microglia are rapidly activated in situ, followed by waves of circulating monocytes into the ischemic area. Activated microglia and monocytes/macrophages are mainly distributed in the peri-infarct area. These cells have similar morphology and functions, such as secreting cytokines and phagocytosis. Previously, the presence of the MPS was considered a marker of an exacerbated inflammatory response that contributes to brain damage. However, recent studies have suggested a rather complicated role of the MPS in IS. Here, we reviewed articles focusing on various functions of the MPS among different phases of IS, including recruitment, polarization, phagocytosis, angiogenesis, and interaction with other types of cells. Moreover, due to the characteristics of the MPS, we also noted clinical research addressing alterations in the MPS as potential biomarkers for IS patients for the purposes of predicting prognosis and developing novel therapeutic strategies.
Topics: Humans; Ischemic Stroke; Mononuclear Phagocyte System; Macrophages; Microglia; Monocytes; Stroke
PubMed: 36755470
DOI: 10.1111/bpa.13151 -
Immunological Investigations Oct 2020Phosphatidylserine (PS) is a naturally occurring anionic phospholipid that is primarily located in the inner leaflet of eukaryotic cell membranes. The role of PS during... (Review)
Review
Phosphatidylserine (PS) is a naturally occurring anionic phospholipid that is primarily located in the inner leaflet of eukaryotic cell membranes. The role of PS during apoptosis is one of the most studied biological functions of PS. Externalization of PS during apoptosis mediates an "eat me" signal for phagocytic uptake, leading to clearance of apoptotic cells and thus maintain self-tolerance by immunological ignorance. However, an emerging view is that PS exposure-mediated cellular uptake is not an immunologically silent event, but rather promoting an active tolerance towards self and foreign proteins. This biological property of PS has been exploited by parasites and viruses in order to evade immune surveillance of the host immune system. Further, this novel immune regulatory property of PS that results in tolerance induction can be harnessed for clinical applications, such as to treat autoimmune conditions and to reduce immunogenicity of therapeutic proteins. This review attempts to provide an overview of the biological functions of PS in the immune response and its potential therapeutic applications.
Topics: Animals; Apoptosis; Drug Design; Drug Development; Humans; Immunotherapy; Molecular Structure; Nanoparticles; Phagocytes; Phagocytosis; Phosphatidylserines; Theranostic Nanomedicine
PubMed: 32204629
DOI: 10.1080/08820139.2020.1738456 -
Microbial Phagocytic Receptors and Their Potential Involvement in Cytokine Induction in Macrophages.Frontiers in Immunology 2021Phagocytosis is an essential process for the uptake of large (>0.5 µm) particulate matter including microbes and dying cells. Specialized cells in the body perform... (Review)
Review
Phagocytosis is an essential process for the uptake of large (>0.5 µm) particulate matter including microbes and dying cells. Specialized cells in the body perform phagocytosis which is enabled by cell surface receptors that recognize and bind target cells. Professional phagocytes play a prominent role in innate immunity and include macrophages, neutrophils and dendritic cells. These cells display a repertoire of phagocytic receptors that engage the target cells directly, or indirectly opsonins, to mediate binding and internalization of the target into a phagosome. Phagosome maturation then proceeds to cause destruction and recycling of the phagosome contents. Key subsequent events include antigen presentation and cytokine production to alert and recruit cells involved in the adaptive immune response. Bridging the innate and adaptive immunity, macrophages secrete a broad selection of inflammatory mediators to orchestrate the type and magnitude of an inflammatory response. This review will focus on cytokines produced by NF-κB signaling which is activated by extracellular ligands and serves a master regulator of the inflammatory response to microbes. Macrophages secrete pro-inflammatory cytokines including TNFα, IL1β, IL6, IL8 and IL12 which together increases vascular permeability and promotes recruitment of other immune cells. The major anti-inflammatory cytokines produced by macrophages include IL10 and TGFβ which act to suppress inflammatory gene expression in macrophages and other immune cells. Typically, macrophage cytokines are synthesized, trafficked intracellularly and released in response to activation of pattern recognition receptors (PRRs) or inflammasomes. Direct evidence linking the event of phagocytosis to cytokine production in macrophages is lacking. This review will focus on cytokine output after engagement of macrophage phagocytic receptors by particulate microbial targets. Microbial receptors include the PRRs: Toll-like receptors (TLRs), scavenger receptors (SRs), C-type lectin and the opsonic receptors. Our current understanding of how macrophage receptor stimulation impacts cytokine production is largely based on work utilizing soluble ligands that are destined for endocytosis. We will instead focus this review on research examining receptor ligation during uptake of particulate microbes and how this complex internalization process may influence inflammatory cytokine production in macrophages.
Topics: Animals; Antigens, Bacterial; Cytokines; Humans; Immunity, Innate; Macrophages; Mice; NF-kappa B p50 Subunit; Phagocytes; Phagocytosis; Phagosomes; Signal Transduction; Toll-Like Receptors
PubMed: 33995386
DOI: 10.3389/fimmu.2021.662063 -
Frontiers in Immunology 2021The rapid and efficient phagocytic clearance of apoptotic cells, termed efferocytosis, is a critical mechanism in the maintenance of tissue homeostasis. Removal of... (Review)
Review
The rapid and efficient phagocytic clearance of apoptotic cells, termed efferocytosis, is a critical mechanism in the maintenance of tissue homeostasis. Removal of apoptotic cells through efferocytosis prevents secondary necrosis and the resultant inflammation caused by the release of intracellular contents. The importance of efferocytosis in homeostasis is underscored by the large number of inflammatory and autoimmune disorders, including atherosclerosis and systemic lupus erythematosus, that are characterized by defective apoptotic cell clearance. Although mechanistically similar to the phagocytic clearance of pathogens, efferocytosis differs from phagocytosis in that it is immunologically silent and induces a tissue repair response. Efferocytes face unique challenges resulting from the internalization of apoptotic cells, including degradation of the apoptotic cell, dealing with the extra metabolic load imposed by the processing of apoptotic cell contents, and the coordination of an anti-inflammatory, pro-tissue repair response. This review will discuss recent advances in our understanding of the cellular response to apoptotic cell uptake, including trafficking of apoptotic cell cargo and antigen presentation, signaling and transcriptional events initiated by efferocytosis, the coordination of an anti-inflammatory response and tissue repair, unique cellular metabolic responses and the role of efferocytosis in host defense. A better understanding of how efferocytic cells respond to apoptotic cell uptake will be critical in unraveling the complex connections between apoptotic cell removal and inflammation resolution and maintenance of tissue homeostasis.
Topics: Antigen Presentation; Apoptosis; Gene Expression Regulation; Homeostasis; Humans; Inflammation; Phagocytes; Phagocytosis; Phagosomes; Signal Transduction
PubMed: 33959122
DOI: 10.3389/fimmu.2021.631714 -
Cell Host & Microbe May 2023Treating and preventing infections by antimicrobial-resistant bacterial pathogens is a worldwide problem. Pathogens such as Staphylococcus aureus produce an array of...
Treating and preventing infections by antimicrobial-resistant bacterial pathogens is a worldwide problem. Pathogens such as Staphylococcus aureus produce an array of virulence determinants, making it difficult to identify single targets for the development of vaccines or monoclonal therapies. We described a human-derived anti-S. aureus monoclonal antibody (mAb)-centyrin fusion protein ("mAbtyrin") that simultaneously targets multiple bacterial adhesins, resists proteolysis by bacterial protease GluV8, avoids Fc engagement by S. aureus IgG-binding proteins SpA and Sbi, and neutralizes pore-forming leukocidins via fusion with anti-toxin centyrins, while maintaining Fc- and complement-mediated functions. Compared with the parental mAb, mAbtyrin protected human phagocytes and boosted phagocyte-mediated killing. The mAbtyrin also reduced pathology, reduced bacterial burden, and protected from different types of infections in preclinical animal models. Finally, mAbtyrin synergized with vancomycin, enhancing pathogen clearance in an animal model of bacteremia. Altogether, these data establish the potential of multivalent mAbs for treating and preventing S. aureus diseases.
Topics: Animals; Humans; Staphylococcus aureus; Staphylococcal Infections; Antibodies, Monoclonal; Phagocytes; Leukocidins; Methicillin-Resistant Staphylococcus aureus
PubMed: 37098341
DOI: 10.1016/j.chom.2023.04.004 -
Frontiers in Cellular and Infection... 2020The fungal pathogen can cause life-threatening infections in immune compromised individuals. This pathogen is typically acquired via inhalation, and enters the... (Review)
Review
The fungal pathogen can cause life-threatening infections in immune compromised individuals. This pathogen is typically acquired via inhalation, and enters the respiratory tract. Innate immune cells such as macrophages and dendritic cells (DCs) are the first host cells that encounter , and the interactions between and innate immune cells play a critical role in the progression of disease. possesses several virulence factors and evasion strategies to prevent its killing and destruction by pulmonary phagocytes, but these phagocytic cells can also contribute to anti-cryptococcal responses. This review will focus on the interactions between and primary macrophages and dendritic cells (DCs), dealing specifically with the cryptococcal/pulmonary cell interface.
Topics: Cryptococcosis; Cryptococcus neoformans; Dendritic Cells; Humans; Macrophages; Macrophages, Alveolar
PubMed: 32117810
DOI: 10.3389/fcimb.2020.00037 -
Mucosal Immunology Apr 2022In tissue, mononuclear phagocytes (MNP) are comprised of Langerhans cells, dendritic cells, macrophages and monocyte-derived cells. They are the first immune cells to... (Review)
Review
In tissue, mononuclear phagocytes (MNP) are comprised of Langerhans cells, dendritic cells, macrophages and monocyte-derived cells. They are the first immune cells to encounter HIV during transmission and transmit the virus to CD4 T cells as a consequence of their antigen presenting cell function. To understand the role these cells play in transmission, their phenotypic and functional characterisation is important. With advancements in high parameter single cell technologies, new MNPs subsets are continuously being discovered and their definition and classification is in a state of flux. This has important implications for our knowledge of HIV transmission, which requires a deeper understanding to design effective vaccines and better blocking strategies. Here we review the historical research of the role MNPs play in HIV transmission up to the present day and revaluate these studies in the context of our most recent understandings of the MNP system.
Topics: CD4-Positive T-Lymphocytes; Dendritic Cells; HIV Infections; Humans; Langerhans Cells; Macrophages; Mononuclear Phagocyte System; Phagocytes
PubMed: 35173293
DOI: 10.1038/s41385-022-00492-0 -
Nature Metabolism Feb 2021Proregenerative responses are required for the restoration of nervous-system functionality in demyelinating diseases such as multiple sclerosis (MS). Yet, the limiting...
Proregenerative responses are required for the restoration of nervous-system functionality in demyelinating diseases such as multiple sclerosis (MS). Yet, the limiting factors responsible for poor CNS repair are only partially understood. Here, we test the impact of a Western diet (WD) on phagocyte function in a mouse model of demyelinating injury that requires microglial innate immune function for a regenerative response to occur. We find that WD feeding triggers an ageing-related, dysfunctional metabolic response that is associated with impaired myelin-debris clearance in microglia, thereby impairing lesion recovery after demyelination. Mechanistically, we detect enhanced transforming growth factor beta (TGFβ) signalling, which suppresses the activation of the liver X receptor (LXR)-regulated genes involved in cholesterol efflux, thereby inhibiting phagocytic clearance of myelin and cholesterol. Blocking TGFβ or promoting triggering receptor expressed on myeloid cells 2 (TREM2) activity restores microglia responsiveness and myelin-debris clearance after demyelinating injury. Thus, we have identified a druggable microglial immune checkpoint mechanism regulating the microglial response to injury that promotes remyelination.
Topics: Aging; Animals; Cholesterol; Demyelinating Diseases; Diet; Diet, Western; Immunity, Innate; Liver X Receptors; Lysophosphatidylcholines; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Microglia; Myelin Sheath; Phagocytes; Receptors, Immunologic; Transforming Growth Factor beta
PubMed: 33619376
DOI: 10.1038/s42255-021-00341-7 -
Cellular and Molecular Gastroenterology... 2020
Topics: Dysbiosis; Humans; Immunity, Innate; Inflammatory Bowel Diseases; Mucous Membrane; Phagocytes
PubMed: 31866400
DOI: 10.1016/j.jcmgh.2019.11.015