Emerging roles for platelets as immune and inflammatory cells

AbstractDespite their small size and anucleate status, platelets have diverse roles in vascular biology. Not only are platelets the cellular mediator of thrombosis, but platelets are also immune cells that initiate and accelerate many vascular inflammatory conditions. Platelets are linked to the pathogenesis of inflammatory diseases such as atherosclerosis, malaria infection, transplant rejection, and rheumatoid arthritis. In some contexts, platelet immune functions are protective, whereas in others platelets contribute to adverse inflammatory outcomes. In this review, we will discuss platelet and platelet-derived mediator interactions with the innate and acquired arms of the immune system and platelet-vessel wall interactions that drive inflammatory disease. There have been many recent publications indicating both important protective and adverse roles for platelets in infectious disease. Because of this new accumulating data, and the fact that infectious disease continues to be a leading cause of death globally, we will also focus on new and emerging concepts related to platelet immune and inflammatory functions in the context of infectious disease.

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Role of neutrophils in tuberculosis: A bird's eye view

Innate Immunity ◽

10.1177/1753425919881176 ◽

2019 ◽

Vol 26 (4) ◽

pp. 240-247

Author(s):

J Nancy Hilda ◽

Sulochana Das ◽

Srikanth P Tripathy ◽

Luke Elizabeth Hanna

Keyword(s):

Immune Cells ◽

Mycobacterial Infection ◽

Host Cells ◽

Immune Functions ◽

Dual Nature ◽

Active Pulmonary Tuberculosis ◽

Inflammatory Conditions ◽

Wide Range ◽

Blood Neutrophils

Neutrophils are innate immune cells implicated in the process of killing Mycobacterium tuberculosis early during infection. Once the mycobacteria enter the human system, neutrophils sense and engulf them. By secreting bactericidal enzymes and α-defensins like human neutrophil peptides loaded in their granule armory, neutrophils kill the pathogen. Peripheral blood neutrophils secrete a wide range of cytokines like IL-8, IL-1-β and IFN-γ in response to mycobacterial infection. Thus they signal and activate distant immune cells thereby informing them of prevailing infection. The activated monocytes, dendritic cells and T cells further continue the immune response. As a final call, neutrophils release neutrophil extracellular traps in circulation which can trap mycobacteria in patients with active pulmonary tuberculosis. Extensive neutrophilic response is associated with inflammation, pulmonary destruction, and pathology. For example, inappropriate phagocytosis of mycobacteria-infected neutrophils can damage host cells due to necrosis of neutrophils, leading to chronic inflammation and tissue damage. This dual nature of neutrophils makes them double-edged swords during tuberculosis, and hence data available on neutrophil functions against mycobacterium are controversial and non-uniform. This article reviews the role of neutrophils in tuberculosis infection and highlights research gaps that need to be addressed. We focus on our understanding of new research ideologies targeting neutrophils (a) in the early stages of infection for boosting specific immune functions or (b) in the later stages of infection to prevent inflammatory conditions mediated by activated neutrophils. This would plausibly lead to the development of better tuberculosis vaccines and therapeutics in the future.

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The Trypanosoma brucei-Derived Ketoacids, Indole Pyruvate and Hydroxyphenylpyruvate, Induce HO-1 Expression and Suppress Inflammatory Responses in Human Dendritic Cells

Antioxidants ◽

10.3390/antiox11010164 ◽

2022 ◽

Vol 11 (1) ◽

pp. 164

Author(s):

Hannah K. Fitzgerald ◽

Sinead A. O’Rourke ◽

Eva Desmond ◽

Nuno G. B. Neto ◽

Michael G. Monaghan ◽

...

Keyword(s):

Dendritic Cells ◽

Trypanosoma Brucei ◽

Immune Cells ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Heme Oxygenase 1 ◽

Inflammatory Conditions ◽

High Concentrations ◽

Inflammatory Profile ◽

Human Dendritic Cells

The extracellular parasite and causative agent of African sleeping sickness Trypanosoma brucei (T. brucei) has evolved a number of strategies to avoid immune detection in the host. One recently described mechanism involves the conversion of host-derived amino acids to aromatic ketoacids, which are detected at relatively high concentrations in the bloodstream of infected individuals. These ketoacids have been shown to directly suppress inflammatory responses in murine immune cells, as well as acting as potent inducers of the stress response enzyme, heme oxygenase 1 (HO-1), which has proven anti-inflammatory properties. The aim of this study was to investigate the immunomodulatory properties of the T. brucei-derived ketoacids in primary human immune cells and further examine their potential as a therapy for inflammatory diseases. We report that the T. brucei-derived ketoacids, indole pyruvate (IP) and hydroxyphenylpyruvate (HPP), induce HO-1 expression through Nrf2 activation in human dendritic cells (DC). They also limit DC maturation and suppress the production of pro-inflammatory cytokines, which, in turn, leads to a reduced capacity to differentiate adaptive CD4+ T cells. Furthermore, the ketoacids are capable of modulating DC cellular metabolism and suppressing the inflammatory profile of cells isolated from patients with inflammatory bowel disease. This study therefore not only provides further evidence of the immune-evasion mechanisms employed by T. brucei, but also supports further exploration of this new class of HO-1 inducers as potential therapeutics for the treatment of inflammatory conditions.

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Enigma of IL-17 and Th17 Cells in Rheumatoid Arthritis and in Autoimmune Animal Models of Arthritis

Mediators of Inflammation ◽

10.1155/2016/6145810 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 36

Author(s):

Reka Kugyelka ◽

Zoltan Kohl ◽

Katalin Olasz ◽

Katalin Mikecz ◽

Tibor A. Rauch ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Animal Models ◽

Immune Cells ◽

Th17 Cells ◽

Inflammatory Diseases ◽

Joint Destruction ◽

Rodent Models ◽

Immune Functions

Rheumatoid arthritis (RA) is one of the most common autoimmune disorders characterized by the chronic and progressive inflammation of various organs, most notably the synovia of joints leading to joint destruction, a shorter life expectancy, and reduced quality of life. Although we have substantial information about the pathophysiology of the disease with various groups of immune cells and soluble mediators identified to participate in the pathogenesis, several aspects of the altered immune functions and regulation in RA remain controversial. Animal models are especially useful in such scenarios. Recently research focused on IL-17 and IL-17 producing cells in various inflammatory diseases such as in RA and in different rodent models of RA. These studies provided occasionally contradictory results with IL-17 being more prominent in some of the models than in others; the findings of such experimental setups were sometimes inconclusive compared to the human data. The aim of this review is to summarize briefly the recent advancements on the role of IL-17, particularly in the different rodent models of RA.

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Hyperferritinaemia: An Iron Sword of Autoimmunity

Current Pharmaceutical Design ◽

10.2174/1381612825666190709202804 ◽

2019 ◽

Vol 25 (27) ◽

pp. 2909-2918 ◽

Cited By ~ 4

Author(s):

Joanna Giemza-Stokłosa ◽

Md. Asiful Islam ◽

Przemysław J. Kotyla

Keyword(s):

Immune Response ◽

Macrophage Activation ◽

Inflammatory Diseases ◽

Acute Phase Reactant ◽

Catastrophic Antiphospholipid Syndrome ◽

Inflammatory Conditions ◽

Phase Reactant ◽

Signalling Molecule ◽

Cytokine Synthesis

Background:: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Methods:: Different electronic databases were searched in a non-systematic way to find out the literature of interest. Results:: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still’s diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. Conclusion:: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

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Salivary mir-27b Expression in Oral Lichen Planus Patients: A Series of Cases and a Narrative Review of Literature

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191121144407 ◽

2020 ◽

Vol 19 (31) ◽

pp. 2816-2823 ◽

Cited By ~ 3

Author(s):

Dario Di Stasio ◽

Laura Mosca ◽

Alberta Lucchese ◽

Donatella Delle Cave ◽

Hiromichi Kawasaki ◽

...

Keyword(s):

Lichen Planus ◽

Oral Lichen Planus ◽

Inflammatory Diseases ◽

Biological Fluids ◽

Critical Role ◽

Invasive Procedure ◽

Control Group ◽

Study Group ◽

Immune Functions ◽

Oral Lichen

Background: microRNAs play a critical role in auto-immunity, cell proliferation, differentiation and cell death. miRNAs are present in all biological fluids, and their expression is essential in maintaining regular immune functions and preventing autoimmunity, whereas miRNA dysregulation may be associated with the pathogenesis of autoimmune and inflammatory diseases. Oral lichen planus (OLP) is an inflammatory disease mediated by cytotoxic T cells attack against epithelial cells. The present study aims to perform a specific microRNA expression profile through the analysis of saliva in this disease. Methods: The study group was formed by five patients (mean age 62.8±1.98 years; 3 females/2 males) affected by oral lichen planus and control group by five healthy subjects (mean age 59.8 years±2.3; 3 females/ 2 males); using a low-density microarray analysis, we recorded a total of 98 differentially expressed miRNAs in the saliva of patients with oral lichen planus compared to the control group. The validation was performed for miR-27b with qRT-PCR in all saliva samples of oral lichen planus group. Results: 89 miRNAs were up-regulated and nine down-regulated. In details, levels of miR-21, miR- 125b, miR-203 and miR15b were increased (p<0.001) in study group while levels of miR-27b were about 3.0-fold decreased compared to controls (p<0.001) of miR-27b expression in OLP saliva. QRTPCR validation confirmed the down regulation of miR-27b in all saliva samples. Conclusions: Collecting saliva samples is a non-invasive procedure and is well accepted by all patients. microRNAs can be readily isolated and identified and can represent useful biomarkers of OLP.

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Increased Circulatory Extrarenal 1α,25-Dihydroxyvitamin D3 in Bilaterally Nephrectomized Rats

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200530222426 ◽

2020 ◽

Vol 20 (9) ◽

pp. 1523-1530

Author(s):

Murat Dabak ◽

Durrin O. Dabak ◽

Tuncay Kuloglu ◽

Ersoy Baydar ◽

Hakan Bulut ◽

...

Keyword(s):

Immune Cells ◽

Low Dose ◽

Systemic Circulation ◽

Bilateral Nephrectomy ◽

Dihydroxyvitamin D3 ◽

Hydroxyvitamin D ◽

Inflammatory Conditions ◽

Calcium Phosphorus ◽

25 Hydroxyvitamin D

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. Conclusions: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.

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Platelets: Angels and demons dancing on the immune stage. Nutrition conducts the orchestra

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200901183119 ◽

2020 ◽

Vol 20 ◽

Author(s):

Thea Magrone ◽

Manrico Magrone ◽

Matteo Antonio Russo ◽

Emilio Jirillo

Keyword(s):

Platelet Function ◽

Immune Cells ◽

Dual Role ◽

Immune Functions ◽

Omega 3 ◽

Adaptive Immune ◽

Cytokines And Chemokines ◽

Adaptive Immune Cells ◽

Immune Mediated ◽

Inflammatory Processes

Background: Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. Objectives: The participation of platelets in inflammatory processes will be discussed also in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Conclusion: Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.

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Platelet-vessel wall interactions: Implication of 5-hydroxytryptamine. A review

Agents and Actions ◽

10.1007/bf01966783 ◽

1984 ◽

Vol 15 (5-6) ◽

pp. 612-626 ◽

Cited By ~ 54

Author(s):

F. Clerck ◽

J. M. Nueten ◽

R. S. Reneman

Keyword(s):

Vessel Wall ◽

Wall Interactions

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How Changes in the Nutritional Landscape Shape Gut Immunometabolism

Nutrients ◽

10.3390/nu13030823 ◽

2021 ◽

Vol 13 (3) ◽

pp. 823

Author(s):

Jian Tan ◽

Duan Ni ◽

Rosilene V. Ribeiro ◽

Gabriela V. Pinget ◽

Laurence Macia

Keyword(s):

Immune Cells ◽

Metabolic Pathways ◽

Immune Cell ◽

Food Additives ◽

Cell Activity ◽

Inflammatory Cells ◽

Therapeutic Approaches ◽

Food Antigens ◽

And Function ◽

Micro Organisms

Cell survival, proliferation and function are energy-demanding processes, fuelled by different metabolic pathways. Immune cells like any other cells will adapt their energy production to their function with specific metabolic pathways characteristic of resting, inflammatory or anti-inflammatory cells. This concept of immunometabolism is revolutionising the field of immunology, opening the gates for novel therapeutic approaches aimed at altering immune responses through immune metabolic manipulations. The first part of this review will give an extensive overview on the metabolic pathways used by immune cells. Diet is a major source of energy, providing substrates to fuel these different metabolic pathways. Protein, lipid and carbohydrate composition as well as food additives can thus shape the immune response particularly in the gut, the first immune point of contact with food antigens and gastrointestinal tract pathogens. How diet composition might affect gut immunometabolism and its impact on diseases will also be discussed. Finally, the food ingested by the host is also a source of energy for the micro-organisms inhabiting the gut lumen particularly in the colon. The by-products released through the processing of specific nutrients by gut bacteria also influence immune cell activity and differentiation. How bacterial metabolites influence gut immunometabolism will be covered in the third part of this review. This notion of immunometabolism and immune function is recent and a deeper understanding of how lifestyle might influence gut immunometabolism is key to prevent or treat diseases.

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Illuminating an Invisible Epidemic: A Systemic Review of the Clinical and Economic Benefits of Early Diagnosis and Treatment in Inflammatory Disease and Related Syndromes

Journal of Clinical Medicine ◽

10.3390/jcm8040493 ◽

2019 ◽

Vol 8 (4) ◽

pp. 493 ◽

Cited By ~ 1

Author(s):

Wylezinski ◽

Gray ◽

Polk ◽

Harmata ◽

Spurlock

Keyword(s):

Healthcare System ◽

Inflammatory Diseases ◽

The United States ◽

Economic Benefits ◽

Systemic Review ◽

Best Interest ◽

Delayed Treatment ◽

Inflammatory Conditions ◽

Slow Development ◽

The U.S

Healthcare expenditures in the United States are growing at an alarming level with the Centers for Medicare and Medicaid Services (CMS) projecting that they will reach $5.7 trillion per year by 2026. Inflammatory diseases and related syndromes are growing in prevalence among Western societies. This growing population that affects close to 60 million people in the U.S. places a significant burden on the healthcare system. Characterized by relatively slow development, these diseases and syndromes prove challenging to diagnose, leading to delayed treatment against the backdrop of inevitable disability progression. Patients require healthcare attention but are initially hidden from clinician’s view by the seemingly generalized, non-specific symptoms. It is imperative to identify and manage these underlying conditions to slow disease progression and reduce the likelihood that costly comorbidities will develop. Enhanced diagnostic criteria coupled with additional technological innovation to identify inflammatory conditions earlier is necessary and in the best interest of all healthcare stakeholders. The current total cost to the U.S. healthcare system is at least $90B dollars annually. Through unique analysis of financial cost drivers, this review identifies opportunities to improve clinical outcomes and help control these disease-related costs by 20% or more.

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