scholarly journals Small molecules, big effects: microbial metabolites in intestinal immunity

2020 ◽  
Vol 318 (5) ◽  
pp. G907-G911
Author(s):  
Lila G. Glotfelty ◽  
Andrea C. Wong ◽  
Maayan Levy
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Microbial Community ◽  
Small Molecules ◽  
Defense Mechanisms ◽  
Microbial Metabolites ◽  
Intestinal Immunity ◽  
Vast Number ◽  
Health And Disease ◽  
Mammalian Intestine

The mammalian intestine is host to a vast number of microbial organisms. The immune system must balance tolerance with innate and adaptive defense mechanisms to maintain homeostasis with the microbial community. Interestingly, microbial metabolites have been shown to play a role in shaping the host immune response, thus assisting with adaptations that have significant implications for human health and disease. New investigations have uncovered roles for metabolites in modulating almost every aspect of the immune system. In this minireview, we survey these recent findings, which taken together reveal nuanced interactions that we are just beginning to understand.

scholarly journals Role of 5-HT7 receptors in the immune system in health and disease

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Alejandro Quintero-Villegas ◽  
Sergio Iván Valdés-Ferrer
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Immune System ◽  
Blood Platelets ◽  
Pain Tolerance ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Health And Disease

AbstractIn mammalians, serotonin (5-HT) has critical roles in the central nervous system (CNS), including mood stability, pain tolerance, or sleep patterns. However, the vast majority of serotonin is produced by intestinal enterochromaffin cells of the gastrointestinal tract and circulating blood platelets, also acting outside of the CNS. Serotonin effects are mediated through its interaction with 5-HT receptors (5-HTRs), a superfamily with a repertoire of at least fourteen well-characterized members. 5-HT7 receptors are the last 5-HTR member to be identified, with well-defined functions in the nervous, gastrointestinal, and vascular systems. The effects of serotonin on the immune response are less well understood. Mast cells are known to produce serotonin, while T cells, dendritic cells, monocytes, macrophages and microglia express 5-HT7 receptor. Here, we review the known roles of 5-HT7 receptors in the immune system, as well as their potential therapeutic implication in inflammatory and immune-mediated disorders.

scholarly journals Hybrid Nanogels: Stealth and Biocompatible Structures for Drug Delivery Applications

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 71 ◽  
Author(s):  
Parisa Eslami ◽  
Filippo Rossi ◽  
Stefano Fedeli
Keyword(s):  
Drug Delivery ◽  
Immune Response ◽  
Immune System ◽  
Defense Mechanisms ◽  
Biomedical Applications ◽  
The Self ◽  
Host Organism ◽  
Zwitterionic Polymers ◽  
Self Defense ◽  
Polymeric Structures

Considering nanogels, we have focused our attention on hybrid nanosystems for drug delivery and biomedical purposes. The distinctive strength of these structures is the capability to join the properties of nanosystems with the polymeric structures, where versatility is strongly demanded for biomedical applications. Alongside with the therapeutic effect, a non-secondary requirement of the nanosystem is indeed its biocompatibility. The importance to fulfill this aim is not only driven by the priority to reduce, as much as possible, the inflammatory or the immune response of the organism, but also by the need to improve circulation lifetime, biodistribution, and bioavailability of the carried drugs. In this framework, we have therefore gathered the hybrid nanogels specifically designed to increase their biocompatibility, evade the recognition by the immune system, and overcome the self-defense mechanisms present in the bloodstream of the host organism. The works have been essentially organized according to the hybrid morphologies and to the strategies adopted to fulfill these aims: Nanogels combined with nanoparticles or with liposomes, and involving polyethylene glycol chains or zwitterionic polymers.

scholarly journals Immune response and gut microbial community structure in bumblebees after microbiota transplants

2016 ◽  
Vol 283 (1831) ◽  
pp. 20160312 ◽  
Author(s):  
Kathrin Näpflin ◽  
Paul Schmid-Hempel
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Microbial Community ◽  
Bombus Terrestris ◽  
Microbial Community Composition ◽  
Host Immune System ◽  
Susceptible Host ◽  
Protective Function ◽  
Crithidia Bombi ◽  
Gut Microbial Community

Microbial communities are a key component of host health. As the microbiota is initially ‘foreign’ to a host, the host's immune system should respond to its acquisition. Such variation in the response should relate not only to host genetic background, but also to differences in the beneficial properties of the microbiota. However, little is known about such interactions. Here, we investigate the gut microbiota of the bumblebee, Bombus terrestris , which has a protective function against the bee's natural trypanosome gut parasite, Crithidia bombi . We transplanted ‘resistant’ and ‘susceptible’ microbiota into ‘resistant’ and ‘susceptible’ host backgrounds, and studied the activity of the host immune system. We found that bees from different resistance backgrounds receiving a microbiota differed in aspects of their immune response. At the same time, the elicited immune response also depended on the received microbiota's resistance phenotype. Furthermore, the microbial community composition differed between microbiota resistance phenotypes (resistant versus susceptible). Our results underline the complex feedback between the host's ability to potentially exert selection on the establishment of a microbial community and the influence of the microbial community on the host immune response in turn.

scholarly journals Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Phillips-Farfán Bryan ◽  
Carvajal Karla ◽  
Medina-Torres Edgar Alejandro ◽  
Espinosa-Padilla Sara Elva ◽  
Fabrias Gemma ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Therapeutic Agents ◽  
Intestinal Cells ◽  
Intestinal Immunity ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) describes different illnesses characterized by chronic inflammation of the gastrointestinal tract. Although the pathogenic mechanisms leading to IBD are poorly understood, immune system disturbances likely underlie its development. Sphingolipids (SLs) have been identified as important players and promising therapeutic targets to control inflammation in IBD. Interestingly, it seems that microorganisms of the normal gut microbiota and probiotics are involved in sphingolipid function. However, there is a great need to investigate the role of SLs as intermediates in the crosstalk between intestinal immunity and microorganisms. This review focuses on recent investigations that describe some mechanisms involved in the regulation of cytokine profiles by SLs. We also describe the importance of gut microbiota in providing signaling molecules that favor the communication between resident bacteria and intestinal cells. This, in turn, modulates the immune response in the bowel and likely in other peripheral organs. The potential of SLs and gut microbiota as targets or therapeutic agents for IBD is also discussed.

scholarly journals Perspectives in the Application of Immunocorrector – transfer factor ™ in Immunoprophylaxis Programmes and Immunorehabilitation

2019 ◽  
Vol 2 (15) ◽  
Author(s):  
Alexey Ya. Chizhov ◽  
Algimantas Kirkutis ◽  
Jurgita Andruškienė
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Small Molecules ◽  
Human Health ◽  
Transfer Factor ◽  
Cell Mediated Immunity ◽  
Transfer Factors ◽  
Literature Overview ◽  
Somatic Diseases ◽  
New Generation

Background. Human health is largely determined by the body’s resistance to various damaging factors and, in particular, the functional state of its immune system. The use of unique, new generation immunomodulators in prevention of diseases is promising. Goal of the research was to defne the perspectives in the application of immunocorrector Transfer factorTM in immunoprophylaxis programmes and immunorehabilitation analysing and summarizing scientifc articles. Methods. Systemic literature overview was performed, including 77 scientifc articles and conference proceedings in English, published in the period from 1949 to 2016. The main inclusion criterion was clinical trial or literature review, analysing the effect of immunocorrector on human health in cases of different disorders.  Results. Transfer factors are molecules that communicate antigenic immunological information intracellularly from a donor to a recipient. Mammalian Transfer factors, including those of humans are small molecules between 3,500 and 10,000 Daltons. Transfer factor’s functions of cell-mediated immunity and non-specifc immunological activity differ from the functions of antibodies. Transfer factors are divided into three fractions: the inductors that provide rapid immune response and general readiness of the immune system; suppressors, which regulate the intensity of the immune response, preventing allergic and autoimmune reactions; antigen specifc Transfer factors with a set of certain antigens, allowing quick adjusting of the immune system to recognize many bacterial and viruses. Conclusions. Transfer factors have no side effects and are considered as highly effective in treatment of infectious, parasitic, oncological, dermatological, venereal and somatic diseases, so are highly recommended for preventive purposes and decreasing of aging.]Keywords: transfer factor, immunoprophylaxis, immunorehabilitation.

scholarly journals Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore

2021 ◽  
pp. jclinpath-2020-207337
Author(s):  
Claudia Núñez-Torrón ◽  
Ana Ferrer-Gómez ◽  
Esther Moreno Moreno ◽  
Belen Pérez-Mies ◽  
Jesús Villarrubia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune System ◽  
Multiorgan Failure ◽  
Histological Findings ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Bone Marrow Tissue ◽  
Autopsy Findings ◽  
Specific Finding ◽  
Clinical Records

BackgroundSecondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.AimOur objective is to ascertain the existence of sHLH in some patients with severe COVID-19.MethodsWe report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.ResultsEleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.ConclusionsOur results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 380
Author(s):  
Ales Macela ◽  
Klara Kubelkova
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Host Cell ◽  
Critical Role ◽  
Cell Interaction ◽  
Immune Recognition ◽  
Autoantibody Production ◽  
Host Cell Interaction ◽  
Primary Virus

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

scholarly journals MITF induces escape from innate immunity in melanoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Luis Sánchez-del-Campo ◽  
Román Martí-Díaz ◽  
María F. Montenegro ◽  
Rebeca González-Guerrero ◽  
Trinidad Hernández-Caselles ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Nk Cell ◽  
Luciferase Reporter ◽  
Damage Repair ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
Nk Cytotoxicity

Abstract Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

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