Role of pattern-recognition receptors in cardiovascular health and disease

2007 ◽  
Vol 35 (6) ◽  
pp. 1449-1452 ◽  
Author(s):  
J.A. Mitchell ◽  
B. Ryffel ◽  
V.F.J. Quesniaux ◽  
N. Cartwright ◽  
M. Paul-Clark
Keyword(s):  
Pattern Recognition ◽  
Cardiovascular System ◽  
Immune Cells ◽  
Cardiovascular Health ◽  
Cell Function ◽  
Immune Cell ◽  
Pattern Recognition Receptors ◽  
Coagulation System ◽  
Nucleotide Oligomerization ◽  
New Treatments

A role for PRRs (pattern-recognition receptors) in immune cell function is now well established. In macrophages and other immune cells, activation of TLRs (Toll-like receptors) and cytosolic NLRs [NOD (nucleotide oligomerization domain) proteins containing a leucine-rich repeat] results in the induction of genes and release of imunoregulator hormones including cytokines and NO (nitric oxide). In addition to immune cells, structural cells of the cardiovascular system including endothelial cells, vascular smooth muscle and cardiac myocytes express functional PRRs and sense PAMPs (pathogen-associated molecular patterns). Furthermore, bacteria and PAMPs activate the coagulation system and platelets. TLRs are now implicated in a range of cardiovascular diseases and syndromes including atherosclerosis and sepsis. Our group is working on the hypotheses that differences exist in how tissues of the cardiovascular system, including vessels, endothelium, heart and blood, sense pathogens compared with immune cells (principally macrophages) and that identifying such differences will reveal new therapeutic targets for the treatment of cardiovascular disease. We have identified examples of similarities and differences in how cardiovascular tissues and macrophages sense PAMPs. These findings will be discussed together with our interpretation of how this information may lead to new treatments.

scholarly journals Critical Analysis of Non-Thermal Plasma-Driven Modulation of Immune Cells from Clinical Perspective

2020 ◽  
Vol 21 (17) ◽  
pp. 6226 ◽  
Author(s):  
Barbora Smolková ◽  
Adam Frtús ◽  
Mariia Uzhytchak ◽  
Mariia Lunova ◽  
Šárka Kubinová ◽  
...  
Keyword(s):  
Immune Cells ◽  
Thermal Plasma ◽  
Critical Analysis ◽  
Cell Function ◽  
Immune Cell ◽  
Real Life ◽  
Research Strategy ◽  
Cellular Mechanisms ◽  
Non Thermal Plasma

The emerged field of non-thermal plasma (NTP) shows great potential in the alteration of cell redox status, which can be utilized as a promising therapeutic implication. In recent years, the NTP field considerably progresses in the modulation of immune cell function leading to promising in vivo results. In fact, understanding the underlying cellular mechanisms triggered by NTP remains incomplete. In order to boost the field closer to real-life clinical applications, there is a need for a critical overview of the current state-of-the-art. In this review, we conduct a critical analysis of the NTP-triggered modulation of immune cells. Importantly, we analyze pitfalls in the field and identify persisting challenges. We show that the identification of misconceptions opens a door to the development of a research strategy to overcome these limitations. Finally, we propose the idea that solving problems highlighted in this review will accelerate the clinical translation of NTP-based treatments.

scholarly journals 58 Functional nutrition to modulate the immune response

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 66-66
Keyword(s):  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Animal Feed ◽  
Consumer Preference ◽  
Companion Animal ◽  
Feed Additives ◽  
Cellular Migration ◽  
Lipid Mediator ◽  
Omega 3

Abstract Growing concerns about antibiotic resistance coupled with recent legislation limiting in-feed antibiotic use in livestock feed has led to a resurgence of interest in plant-based extracts, prebiotics/probiotics, and other nutraceutical compounds with immune-modulating properties. Consumer preference for functional ingredients in their own food as well as feed for their pets or livestock has created a niche for development of feed additives with bioactive properties with the potential to improve health through their ability to regulate inflammation and modulate microbial communities. For example, dietary omega-3 fatty acids have been documented to reduce inflammation through altering the fatty acid composition of immune cells, shifting immune cell function, and reducing inflammatory lipid mediator and cytokine production. Dietary probiotic supplementation allows an intimate interaction between the gut mucosa and the largest concentrated population of the host’s immune cells, the mucosal immune system. Probiotics have been shown to modulate the inflammatory response through interaction with intestinal epithelial cells, M-cells in Peyer’s patches, innate immune cells such as dendritic and other antigen-presenting cells, and increasing barrier function through increased mucus and antibody production. Other feedstuffs such as green tea components (epigallocatechin-3-gallate, EGCG) interact with neutrophils and macrophages to limit cellular migration and inflammatory molecule production to reduce inflammation. A wealth of information detailing mechanistic outcomes exists in mouse literature and human cell lines, while livestock and companion animal literature is an untapped area for future work. An emphasis on research aimed at a more molecular, mechanistic understanding of currently available feed additives will lead to the improvement of existing additives and development of new additives for use in livestock and companion animal feed.

scholarly journals GABAA receptor α4-subunit knockout enhances lung inflammation and airway reactivity in a murine asthma model

2017 ◽  
Vol 313 (2) ◽  
pp. L406-L415 ◽  
Author(s):  
Gene T. Yocum ◽  
Damian L. Turner ◽  
Jennifer Danielsson ◽  
Matthew B. Barajas ◽  
Yi Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Immune Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Asthma Model

Emerging evidence indicates that hypnotic anesthetics affect immune function. Many anesthetics potentiate γ-aminobutyric acid A receptor (GABAAR) activation, and these receptors are expressed on multiple subtypes of immune cells, providing a potential mechanistic link. Like immune cells, airway smooth muscle (ASM) cells also express GABAARs, particularly isoforms containing α4-subunits, and activation of these receptors leads to ASM relaxation. We sought to determine if GABAAR signaling modulates the ASM contractile and inflammatory phenotype of a murine allergic asthma model utilizing GABAAR α4-subunit global knockout (KO; Gabra40/0) mice. Wild-type (WT) and Gabra4 KO mice were sensitized with house dust mite (HDM) antigen or exposed to PBS intranasally 5 days/wk for 3 wk. Ex vivo tracheal rings from HDM-sensitized WT and Gabra4 KO mice exhibited similar magnitudes of acetylcholine-induced contractile force and isoproterenol-induced relaxation ( P = not significant; n = 4). In contrast, in vivo airway resistance (flexiVent) was significantly increased in Gabra4 KO mice ( P < 0.05, n = 8). Moreover, the Gabra4 KO mice demonstrated increased eosinophilic lung infiltration ( P < 0.05; n = 4) and increased markers of lung T-cell activation/memory (CD62L low, CD44 high; P < 0.01, n = 4). In vitro, Gabra4 KO CD4+ cells produced increased cytokines and exhibited increased proliferation after stimulation of the T-cell receptor as compared with WT CD4+ cells. These data suggest that the GABAAR α4-subunit plays a role in immune cell function during allergic lung sensitization. Thus GABAAR α4-subunit-specific agonists have the therapeutic potential to treat asthma via two mechanisms: direct ASM relaxation and inhibition of airway inflammation.

scholarly journals Dysregulation of Systemic Immunity in Aging and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Jenny Lutshumba ◽  
Barbara S. Nikolajczyk ◽  
Adam D. Bachstetter
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Human Subjects ◽  
Brain Inflammation ◽  
Adaptive Immune Cells ◽  
Age Related ◽  
The Brain ◽  
Age Related Changes

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks coupled with more traditional immune system stimuli like infection or injury likely combine to trigger and maintain persistent microglial and thus brain inflammation. This review summarizes age-related changes in immune cell function, with special emphasis on lymphocytes as a source of inflammation, and discusses how such changes may potentiate both systemic and central nervous system inflammation to culminate in dementia. We recap the understudied area of AD-associated changes in systemic lymphocytes in greater detail to provide a unifying perspective of inflammation-fueled dementia, with an eye toward evidence of two-way communication between the brain parenchyma and blood immune cells. We focused our review on human subjects studies, adding key data from animal models as relevant.

scholarly journals Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

2020 ◽  
Vol 8 (24) ◽  
pp. 5195-5203
Author(s):  
Joslyn L. Mangal ◽  
Sahil Inamdar ◽  
Yi Yang ◽  
Subhadeep Dutta ◽  
Mamta Wankhede ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Dendritic Cell ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Dendritic Cell Function ◽  
Cell Functions

Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner modulate the function of the immune cells.

Nanoparticle impact on innate immune cell pattern-recognition receptors and inflammasomes activation

2017 ◽  
Vol 34 ◽  
pp. 3-24 ◽  
Author(s):  
Ana Luísa Silva ◽  
Carina Peres ◽  
João Conniot ◽  
Ana I. Matos ◽  
Liane Moura ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Immune Cell ◽  
Pattern Recognition Receptors ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Cell Pattern

scholarly journals Plasma kallikrein modulates immune cell trafficking during neuroinflammation via PAR2 and bradykinin release

2018 ◽  
Vol 116 (1) ◽  
pp. 271-276 ◽  
Author(s):  
Kerstin Göbel ◽  
Chloi-Magdalini Asaridou ◽  
Monika Merker ◽  
Susann Eichler ◽  
Alexander M. Herrmann ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Cell Function ◽  
Immune Cell ◽  
Cellular Adhesion ◽  
Coagulation System ◽  
Intercellular Adhesion Molecule ◽  
Plasma Kallikrein ◽  
Dependent Manner ◽  
Cns Inflammation ◽  
Endothelial Cell Function

Blood–brain barrier (BBB) disruption and transendothelial trafficking of immune cells into the central nervous system (CNS) are pathophysiological hallmarks of neuroinflammatory disorders like multiple sclerosis (MS). Recent evidence suggests that the kallikrein-kinin and coagulation system might participate in this process. Here, we identify plasma kallikrein (KK) as a specific direct modulator of BBB integrity. Levels of plasma prekallikrein (PK), the precursor of KK, were markedly enhanced in active CNS lesions of MS patients. Deficiency or pharmacologic blockade of PK renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by a remarkable reduction of BBB disruption and CNS inflammation. In vitro analysis revealed that KK modulates endothelial cell function in a protease-activated receptor-2–dependent manner, leading to an up-regulation of the cellular adhesion molecules Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Molecule 1, thereby amplifying leukocyte trafficking. Our study demonstrates that PK is an important direct regulator of BBB integrity as a result of its protease function. Therefore, KK inhibition can decrease BBB damage and cell invasion during neuroinflammation and may offer a strategy for the treatment of MS.

Pathogenesis of ANCA-associated vasculitis: an emerging role for immunometabolism

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_3) ◽  
pp. iii33-iii41
Author(s):  
Emma Leacy ◽  
Gareth Brady ◽  
Mark A Little
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Systemic Autoimmune Disease ◽  
Cellular Activation ◽  
Ample Evidence ◽  
Anca Associated Vasculitis

Abstract ANCA-associated vasculitis (AAV) is a severe systemic autoimmune disease. A key feature of AAV is the presence of Anti-Neutrophil Cytoplasmic Antibodies (ANCA) directed against myeloperoxidase (MPO) or proteinase-3 (PR3). ANCA are key to the pathogenesis of AAV, where they activate innate immune cells to drive inflammation. Pre-activation or ‘priming’ of immune cells appears to be important for complete cellular activation in AAV. The burgeoning field of immunometabolism has illuminated the governance of immune cell function by distinct metabolic pathways. There is ample evidence that the priming events synonymous with AAV alter immune cell metabolism. In this review we discuss the pathogenesis of AAV and its intersection with recent insights into immune cell metabolism.

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