scholarly journals Interleukin-27 and Its Diverse Effects on Bacterial Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Yugo Morita ◽  
Elysia A. Masters ◽  
Edward M. Schwarz ◽  
Gowrishankar Muthukrishnan
Keyword(s):  
Immune Responses ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Chronic Infections ◽  
Cell Functions ◽  
Interleukin 27 ◽  
Life Threatening ◽  
Anti Inflammatory ◽  
Active Research

Innate and adaptive immune responses against pathogens are known to be carefully orchestrated by specific cytokines that initiate and down regulate immune cell functions from the initial infection through tissue repair and homeostasis. However, some cytokines, including interleukin-27, are expressed at multiple phases of the infection, such that their pro and anti-inflammatory functions have been difficult to interpret. As elucidation of specific cytokine functions throughout infection is central to our understanding of protective vs. susceptible immunity and return to homeostasis vs. prolonged inflammation leading to septic shock, here we review the literature on IL-27 signaling and the various functions of this heterodimeric ligand member of the IL-12 cytokine family. Canonically, IL-27 is produced by antigen-presenting cells, and is thought of as an immunostimulatory cytokine due to its capacity to induce Th1 differentiation. However, many studies have also identified various immunosuppressive effects of IL-27 signaling, including suppression of Th17 differentiation and induction of co-inhibitory receptors on T cells. Thus, the exact role of IL-27 in the context of infectious diseases remains a topic of debate and active research. Additionally, as recent interest has focused on clinical management of acute vs. chronic infections, and life-threatening “cytokine storm” from sepsis, we propose a hypothetical model to explain the biphasic role of IL-27 during the early and late phases of immune responses to reconcile its known pro and anti-inflammatory functions, which could be therapeutically regulated to improve patient outcomes of infection.

scholarly journals IFN-γPriming Effects on the Maintenance of Effector Memory CD4+T Cells and on Phagocyte Function: Evidences from Infectious Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Henrique Borges da Silva ◽  
Raíssa Fonseca ◽  
José M. Alvarez ◽  
Maria Regina D’Império Lima
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Effector Memory ◽  
Innate Immune Cells ◽  
Chronic Infections ◽  
Cell Functions ◽  
Memory Cd4 T Cells

Although it has been established that effector memory CD4+T cells play an important role in the protective immunity against chronic infections, little is known about the exact mechanisms responsible for their functioning and maintenance, as well as their effects on innate immune cells. Here we review recent data on the role of IFN-γpriming as a mechanism affecting both innate immune cells and effector memory CD4+T cells. Suboptimal concentrations of IFN-γare seemingly crucial for the optimization of innate immune cell functions (including phagocytosis and destruction of reminiscent pathogens), as well as for the survival and functioning of effector memory CD4+T cells. Thus, IFN-γpriming can thus be considered an important bridge between innate and adaptive immunity.

scholarly journals Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Olga Tsave ◽  
Savvas Petanidis ◽  
Efrosini Kioseoglou ◽  
Maria P. Yavropoulou ◽  
John G. Yovos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Chemical Reactivity ◽  
Inflammatory Cells ◽  
T Cell Signaling ◽  
Cell Immunotherapy ◽  
Molecular Immunology ◽  
Anti Inflammatory

Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs.

scholarly journals Selenium, Selenoproteins, and Immunity

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1203 ◽  
Author(s):  
Joseph Avery ◽  
Peter Hoffmann
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
High Throughput ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Biological Effects ◽  
Cell Functions ◽  
Experimental Systems ◽  
Physiological Processes

Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.

scholarly journals Mechanoimmunology: molecular-scale forces govern immune cell functions

2018 ◽  
Vol 29 (16) ◽  
pp. 1919-1926 ◽  
Author(s):  
Sophie V. Pageon ◽  
Matt A. Govendir ◽  
Daryan Kempe ◽  
Maté Biro
Keyword(s):  
Immune Responses ◽  
Cell Activation ◽  
Immune Cell ◽  
Imaging Techniques ◽  
Mechanical Forces ◽  
The Novel ◽  
Cell Functions ◽  
Immune Cell Activation ◽  
Receptor Interactions

Immune cell recognition of antigens is a pivotal process in initiating immune responses against injury, pathogens, and cancers. Breakthroughs over the past decade support a major role for mechanical forces in immune responses, laying the foundation for the emerging field of mechanoimmunology. In this Perspective, we discuss the mechanical forces acting at the level of ligand–receptor interactions and how they underpin receptor triggering, signal initiation, and immune cell activation. We also highlight the novel biophysical tools and advanced imaging techniques that have afforded us the recent progress in our understanding of the role of forces in immune cell functions.

scholarly journals Exosome: The Regulator of the Immune System in Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Qiu ◽  
Jing Zhou ◽  
Jin Zhang ◽  
Youjing Dong ◽  
Yang Liu
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Disorders ◽  
Life Threatening ◽  
Novel Target ◽  
Organ Dysfunctions ◽  
Body Response

Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. There is growing evidence that the immune system plays a core role in sepsis. Pathogens cause abnormal host immune response and eventually lead to immunosuppression, which is an important cause of death in patients with sepsis. Exosomes are vesicles derived from double invagination of plasma membrane, associating with immune responses closely. The cargos delivered by exosomes into recipient cells, especially immune cells, effectively alter their response and functions in sepsis. In this review, we focus on the effects and mechanisms of exosomes on multiple immune cells, as well as the role of immune cell-derived exosomes in sepsis. This is helpful for us to have an in-depth understanding of the mechanism of immune disorders in sepsis. Exosomes is also expected to become a novel target and therapeutic approach for sepsis.

scholarly journals Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Immune Modulation ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Communication ◽  
Immune Defense ◽  
Research Progress ◽  
Recent Research Progress

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.

scholarly journals The complex functions of microRNA-150 in allergy, autoimmunity and immune tolerance

2021 ◽  
Vol 5 (4) ◽  
pp. 195-221
Author(s):  
Katarzyna Nazimek ◽  
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signaling Cascades ◽  
Cell Functions ◽  
Regulatory Circuits ◽  
Complex Functions ◽  
Genetic Level

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>

scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

The Role of Inflammation in Traumatic Brain Injury

Neurotrauma ◽  
2018 ◽  
pp. 211-232
Author(s):  
Sarah C. Hellewell ◽  
Bridgette D. Semple ◽  
Jenna M. Ziebell ◽  
Nicole Bye ◽  
Cristina Morganti-Kossmann
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Cells ◽  
Immune Cell ◽  
Brain Trauma ◽  
Multiple Roles ◽  
Cell Functions ◽  
Macrophage Populations

Inflammation occurring following brain trauma represents a significant constituent of complex secondary responses that dictate patients’ outcome. Although a few decades have passed since its discovery, new aspects of this intriguing phenomenon are still being uncovered, ranging from the multiple roles of mediators regulating the inception, progression, and resolution of neuroinflammation, to the development of antiinflammatory therapies. This review provides a summary of the vast research on traumatic brain injury inflammation. The authors describe the fundamental aspects of cytokine and immune cell functions, the orchestrated collaboration of chemokines and leukocytes, the phenotypic distinction of macrophage populations, and the contribution of glial cells. Among the beneficial properties of neuroinflammation, they briefly discuss cytokines’ impact on neurogenesis; the chapter concludes by touching on the implications of antiinflammatory therapies.

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

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