scholarly journals Receptors That Inhibit Macrophage Activation: Mechanisms and Signals of Regulation and Tolerance

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Ranferi Ocaña-Guzman ◽  
Luis Vázquez-Bolaños ◽  
Isabel Sada-Ovalle
Keyword(s):  
Immune System ◽  
Cell Lines ◽  
Immune Tolerance ◽  
Defense Mechanisms ◽  
Macrophage Activation ◽  
Immunological Tolerance ◽  
Innate Defense ◽  
Activation Mechanisms ◽  
Monocytes And Macrophages ◽  
Inhibitory Molecules

A variety of receptors perform the function of attenuating or inhibiting activation of cells in which they are expressed. Examples of these kinds of receptors include TIM-3 and PD-1, among others that have been widely studied in cells of lymphoid origin and, though to a lesser degree, in other cell lines. Today, several studies describe the function of these molecules as part of the diverse mechanisms of immune tolerance that exist in the immune system. This review analyzes the function of some of these proteins in monocytes and macrophages and as well as their participation as inhibitory molecules or elements of immunological tolerance that also act in innate defense mechanisms. We chose the receptors TIM-3, PD-1, CD32b, and CD200R because these molecules have distinct functional characteristics that provide examples of the different regulating mechanisms in monocytes and macrophages.

scholarly journals Innate immunity against infectious diseases, particularly in swine

2020 ◽  
Vol 76 (2) ◽  
pp. 67-70
Author(s):  
ZYGMUNT PEJSAK ◽  
MARIAN TRUSZCZYŃSKI ◽  
KAZIMIERZ TARASIUK
Keyword(s):  
Infectious Diseases ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Phagocytic Cells ◽  
Host Defense Peptides ◽  
Innate Defense ◽  
Etiologic Agents ◽  
Monocytes And Macrophages

The importance of innate defense mechanisms especially refering to swine, was characterized. Physical, chemical and microbial barriers were mentioned. The role of cells was underlined in controlling infection by phagocytosis without earlier immunisation by antigens and only depending on the genome of the born animal. The two main types of phagocytic cells were evaluated in antiinfectious activity: a)granular leucocytes, including neutrophils, basophils, eosynophils and mast cells, b)mononuclear phagocytes. These include blood circulating monocytes and macrophages. It was stated that natural killer cells belonging also to innate immune system can kill bacteria and viruses participating as etiologic agents in infectious diseases. Another group of innate immune factors, not cells but molecules, are creating defensins being host defense peptides. The complement mediates the inflammatory response, controlling bacterial infections. The following antiinfectious activity is exerted by Toll-like receptors. The presented cytokines are protein or glycoprotein molecules secreted by cells. They participate in intercellular and intracellular signalling.

scholarly journals Inhibition of Apoptosis by Escherichia coli K1 Is Accompanied by Increased Expression of BclXL and Blockade of Mitochondrial Cytochrome c Release in Macrophages

2004 ◽  
Vol 72 (10) ◽  
pp. 6012-6022 ◽  
Author(s):  
Sunil K. Sukumaran ◽  
Suresh K. Selvaraj ◽  
Nemani V. Prasadarao
Keyword(s):  
Escherichia Coli ◽  
Cell Lines ◽  
Defense Mechanisms ◽  
Mrna Level ◽  
Protein A ◽  
Gene Array ◽  
Macrophage Cell ◽  
Cytochrome C Release ◽  
E Coli ◽  
Monocytes And Macrophages

ABSTRACT Escherichia coli K1 survival in the blood is a critical step for the onset of meningitis in neonates. Therefore, the circulating bacteria are impelled to avoid host defense mechanisms by finding a niche to survive and multiply. Our recent studies have shown that E. coli K1 enters and survives in both monocytes and macrophages in the newborn rat model of meningitis as well as in macrophage cell lines. Here we demonstrate that E. coli K1 not only extends the survival of human and murine infected macrophage cell lines but also renders them resistant to apoptosis induced by staurosporine. Macrophages infected with wild-type E. coli expressing outer membrane protein A (OmpA), but not with OmpA− E. coli, are resistant to DNA fragmentation and phosphatidylserine exposure induced by staurosporine. Infection with OmpA+ E. coli induces the expression of BclXL, an antiapoptotic protein, both at the mRNA level as assessed by gene array analysis and at the protein level as evaluated by immunoblotting. OmpA− E. coli infection of macrophages induced the release of cytochrome c from mitochondria into the cytosol and the activation of caspases 3, 6, and 9, events that were significantly blocked in OmpA+ E. coli-infected macrophages. In addition, OmpA+ E. coli-infected cells were resistant to a decrease in the transmembrane potential of mitochondria induced by staurosporine as measured by the MitoCapture fluorescence technique. Complementation of OmpA− E. coli with a plasmid containing the ompA gene restored the ability of OmpA− E. coli to inhibit the apoptosis of infected macrophages, further demonstrating that E. coli OmpA expression is critical for inducing macrophage survival and thereby finding a safe haven for its growth.

scholarly journals High Innate Immune Specificity through Diversified C-Type Lectin-Like Domain Proteins in Invertebrates

2015 ◽  
Vol 8 (2) ◽  
pp. 129-142 ◽  
Author(s):  
Barbara Pees ◽  
Wentao Yang ◽  
Alejandra Zárate-Potes ◽  
Hinrich Schulenburg ◽  
Katja Dierking
Keyword(s):  
Immune System ◽  
Protein Function ◽  
Innate Immune System ◽  
Defense Mechanisms ◽  
Innate Immune ◽  
Innate Defense ◽  
C Elegans ◽  
Current State ◽  
Gene Diversification

A key question in current immunity research is how the innate immune system can generate high levels of specificity. Evidence is accumulating that invertebrates, which exclusively rely on innate defense mechanisms, can differentiate between pathogens on the species and even strain level. In this review, we identify and discuss the particular potential of C-type lectin-like domain (CTLD) proteins to generate high immune specificity. Whilst several CTLD proteins are known to act as pattern recognition receptors in the vertebrate innate immune system, the exact role of CTLD proteins in invertebrate immunity is much less understood. We show that CTLD genes are highly abundant in most metazoan genomes and summarize the current state of knowledge on CTLD protein function in insect, crustacean and nematode immune systems. We then demonstrate extreme CTLD gene diversification in the genomes of Caenorhabditis nematodes and provide an update of data from CTLD gene function studies in C. elegans, which indicate that the diversity of CTLD genes could contribute to immune specificity. In spite of recent achievements, the exact functions of the diversified invertebrate CTLD genes are still largely unknown. Our review therefore specifically discusses promising research approaches to rectify this knowledge gap.

Immune responses against Marek's disease virus

2010 ◽  
Vol 11 (2) ◽  
pp. 123-134 ◽  
Author(s):  
Payvand Parvizi ◽  
Mohamed Faizal Abdul-Careem ◽  
Kamran Haq ◽  
Niroshan Thanthrige-Don ◽  
Karel A. Schat ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Defense Mechanisms ◽  
Genetic Factors ◽  
Marek's Disease ◽  
Epigenetic Mechanisms ◽  
Marek’S Disease ◽  
First Line ◽  
Soluble Factors ◽  
Innate Defense

AbstractIt is more than a century since Marek's disease (MD) was first reported in chickens and since then there have been concerted efforts to better understand this disease, its causative agent and various approaches for control of this disease. Recently, there have been several outbreaks of the disease in various regions, due to the evolving nature of MD virus (MDV), which necessitates the implementation of improved prophylactic approaches. It is therefore essential to better understand the interactions between chickens and the virus. The chicken immune system is directly involved in controlling the entry and the spread of the virus. It employs two distinct but interrelated mechanisms to tackle viral invasion. Innate defense mechanisms comprise secretion of soluble factors as well as cells such as macrophages and natural killer cells as the first line of defense. These innate responses provide the adaptive arm of the immune system including antibody- and cell-mediated immune responses to be tailored more specifically against MDV. In addition to the immune system, genetic and epigenetic mechanisms contribute to the outcome of MDV infection in chickens. This review discusses our current understanding of immune responses elicited against MDV and genetic factors that contribute to the nature of the response.

scholarly journals Molecular Population Genetics of Drosophila Immune System Genes

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 713-724 ◽  
Author(s):  
Andrew G Clark ◽  
Lei Wang
Keyword(s):  
Immune System ◽  
Defense Mechanisms ◽  
Population Level ◽  
Host Immune System ◽  
Innate Defense ◽  
Evolutionary Forces ◽  
Molecular Population Genetics ◽  
Bactericidal Properties ◽  
Dna Sequence Variation ◽  
High Level

A striking aspect of many vertebrate immune system genes is the exceptionally high level of polymorphism they harbor. A convincing case can be made that this polymorphism is driven by the diversity of pathogens that face selective pressures to evade attack by the host immune system. Different organisms accomplish a defense against diverse pathogens through mechanisms that differ widely in their requirements for specific recognition. It has recently been shown that innate defense mechanisms, which use proteins with broad-spectrum bactericidal properties, are common to both primitive and advanced organisms. In this study we characterize DNA sequence variation in six pathogen defense genes of Drosophila melanogaster and D. mauritiana, including Andropin; cecropin genes CecA1, CecA2, CecB, and CecC; and Diptericin. The necessity for protection against diverse pathogens, which themselves may evolve resistance to insect defenses, motivates a population-level analysis. Estimates of variation levels show that the genes are not exceptionally polymorphic, but Andropin and Diptericin have patterns of variation that differ significantly from neutrality. Patterns of interpopulation and interspecific differentiation also reveal differences among the genes in evolutionary forces.

scholarly journals Toll-like receptors as a potential therapeutic target for atherosclerosis and cardiovascular disease

2018 ◽  
Vol 72 ◽  
pp. 728-739
Author(s):  
Dominika Łacheta ◽  
Wioletta Olejarz ◽  
Małgorzata Wrzosek ◽  
Grażyna Nowicka
Keyword(s):  
Immune System ◽  
Defense Mechanisms ◽  
Host Immune System ◽  
Toll Like Receptors ◽  
Key Factors ◽  
Innate Defense ◽  
Microbial Invasion ◽  
And Migration ◽  
Harmful Effects ◽  
Recognition Receptor

Toll-like receptors belong to the pattern recognition receptor (PRR) group, which plays a major role in maintaining a balance between the host immune system and the microbial invasion. They are key factors in the early, innate defense mechanisms of the immune system, which are manifested by the activation of classical and alternative inflammatory pathways. Excessive activity of these receptors has been shown to cause homeostasis disorders, so that the response of cells with these receptors must be strictly regulated to prevent any harmful effects of their abnormal activation. Thus, cellular responses mediated through TLR receptors have to be strictly regulated in order to prevent potentially harmful effects of their abnormal activation. There is an increasing evidence to suggest, that the Toll-like receptors can initiate and accelerate a development of atherosclerosis. Activation of these receptors leads to enhanced proinflammatory cytokine synthesis, promotes accumulation of foam cells in the aorta and migration of vascular smooth muscle cells from tunica to intima media. The major challenge for development of the TLR blocking drugs is to reduce inflammation without affecting the innate immunity of a body. Although preclinical studies confirm that they are promising therapeutic targets and potential biomarkers in the pathogenesis of atherosclerosis, however it is necessary to fully define their functions.

Interactions between commensal bacteria and the gut-associated immune system of the chicken

2008 ◽  
Vol 9 (1) ◽  
pp. 101-110 ◽  
Author(s):  
Jennifer T. Brisbin ◽  
Joshua Gong ◽  
Shayan Sharif
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Host Response ◽  
Defense Mechanisms ◽  
Regulatory Control ◽  
Host Responses ◽  
Intestinal Damage ◽  
Innate Defense ◽  
Adaptive Immune ◽  
Normal Microbiota

AbstractThe chicken gut-associated lymphoid tissue is made up of a number of tissues and cells that are responsible for generating mucosal immune responses and maintaining intestinal homeostasis. The normal chicken microbiota also contributes to this via the ability to activate both innate defense mechanisms and adaptive immune responses. If left uncontrolled, immune activation in response to the normal microbiota would pose a risk of excessive inflammation and intestinal damage. Therefore, it is important that immune responses to the normal microbiota be under strict regulatory control. Through studies of mammals, it has been established that the mucosal immune system has specialized regulatory and anti-inflammatory mechanisms for eliminating or tolerating the normal microbiota. The mechanisms that exist in the chicken to control host responses to the normal microbiota, although assumed to be similar to that of mammals, have not yet been fully described. This review summarizes what is currently known about the host response to the intestinal microbiota, particularly in the chicken.

scholarly journals An evaluation of the recognised systemic inflammatory biomarkers of chronic sub-optimal inflammation provides evidence for inflammageing (IFA) during multiple sclerosis (MS)

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Christopher Bolton
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Immune Tolerance ◽  
Immunological Tolerance ◽  
Inflammatory Biomarkers ◽  
Compelling Evidence ◽  
Additional Insight ◽  
Demyelinating Disorder ◽  
Insight Into ◽  
Over Time

AbstractThe pathogenesis of the human demyelinating disorder multiple sclerosis (MS) involves the loss of immune tolerance to self-neuroantigens. A deterioration in immune tolerance is linked to inherent immune ageing, or immunosenescence (ISC). Previous work by the author has confirmed the presence of ISC during MS. Moreover, evidence verified a prematurely aged immune system that may change the frequency and profile of MS through an altered decline in immune tolerance. Immune ageing is closely linked to a chronic systemic sub-optimal inflammation, termed inflammageing (IFA), which disrupts the efficiency of immune tolerance by varying the dynamics of ISC that includes accelerated changes to the immune system over time. Therefore, a shifting deterioration in immunological tolerance may evolve during MS through adversely-scheduled effects of IFA on ISC. However, there is, to date, no collective proof of ongoing IFA during MS. The Review addresses the constraint and provides a systematic critique of compelling evidence, through appraisal of IFA-related biomarker studies, to support the occurrence of a sub-optimal inflammation during MS. The findings justify further work to unequivocally demonstrate IFA in MS and provide additional insight into the complex pathology and developing epidemiology of the disease.

scholarly journals CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection

2021 ◽  
Vol 7 (5) ◽  
pp. 382
Author(s):  
Vuvi G. Tran ◽  
Na N. Z. Nguyen ◽  
Byungsuk Kwon
Keyword(s):  
Candida Albicans ◽  
Defense Mechanisms ◽  
Tumor Necrosis ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Wild Type ◽  
Agonistic Antibody ◽  
Innate Defense ◽  
Surface Receptor ◽  
Candida Albicans Infection

Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic C. albican infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, which is encoded by Tnfrsf9, belongs to the tumor necrosis receptor superfamily and has been shown to regulate neutrophils in Gram-positive bacterial infection. Here, we used genetic and immunological tools to probe the involvement of neutrophil CD137 signaling in innate defense mechanisms against systemic C. albicans infection. We first found that Tnfrsf9−/− mice were susceptible to C. albicans infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against C. albicans infection. Priming of isolated neutrophils with anti-CD137 antibody promoted their phagocytic and fungicidal activities through phospholipase C. In addition, injection of anti-CD137 antibody significantly augmented restriction of fungal growth in Tnfrsf9−/− mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance.

scholarly journals An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

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