scholarly journals Innate Immune Cells in Pressure Overload-Induced Cardiac Hypertrophy and Remodeling

2021 ◽  
Vol 9 ◽  
Author(s):  
Xin Liu ◽  
Guo-Ping Shi ◽  
Junli Guo
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mast Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Pressure Overload ◽  
Natural Killer T Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Killer T Cells

Pressure overload and heart failure are among the leading causes of cardiovascular morbidity and mortality. Accumulating evidence suggests that inflammatory cell activation and release of inflammatory mediators are of vital importance during the pathogenesis of these cardiac diseases. Yet, the roles of innate immune cells and subsequent inflammatory events in these processes remain poorly understood. Here, we outline the possible underlying mechanisms of innate immune cell participation, including mast cells, macrophages, monocytes, neutrophils, dendritic cells, eosinophils, and natural killer T cells in these pathological processes. Although these cells accumulate in the atrium or ventricles at different time points after pressure overload, their cardioprotective or cardiodestructive activities differ from each other. Among them, mast cells, neutrophils, and dendritic cells exert detrimental function in experimental models, whereas eosinophils and natural killer T cells display cardioprotective activities. Depending on their subsets, macrophages and monocytes may exacerbate cardiodysfunction or negatively regulate cardiac hypertrophy and remodeling. Pressure overload stimulates the secretion of cytokines, chemokines, and growth factors from innate immune cells and even resident cardiomyocytes that together assist innate immune cell infiltration into injured heart. These infiltrates are involved in pro-hypertrophic events and cardiac fibroblast activation. Immune regulation of cardiac innate immune cells becomes a promising therapeutic approach in experimental cardiac disease treatment, highlighting the significance of their clinical evaluation in humans.

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

Calreticulin Promotes Immunity Against Acute Myeloid Leukemia Cells in Vivo

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 996-996
Author(s):  
Xiufen Chen ◽  
Dominick Fosco ◽  
Douglas E. Kline ◽  
Justin Kline
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Surface ◽  
Vector Control ◽  
Immune Cells ◽  
Myeloid Leukemia ◽  
Innate Immune ◽  
Innate Immune Cells

Abstract Pre-apoptotic cancer cells release internalized calreticulin (CRT) to their surface prior to death, which acts as an ‘eat-me’ signal to local phagocytes. Chemotherapy and irradiation, which can induce immunogenic cell death through CRT translocation, can also result in local and/or systemic immune suppression in the host. To bypass the requirement of exposing the host to chemotherapy to induce translocation of CRT to the cell surface, murine acute myeloid leukemia (AML) cells (C1498), were engineered to constitutively express cell surface CRT (C1498.CRT). Vector control C1498 or C1498.CRT cells were inoculated intravenously (IV) into C57BL/6 mice. Significantly prolonged survival was observed in hosts harboring C1498.CRT versus vector control C1498 cells systemically. The survival benefit were abrogated in both Rag2-/- hosts or by depletion of T cells with anti-CD4 plus anti-CD8 antibodies, arguing that the immune-mediated effect of cell-surface CRT expression is dependent upon a functional adaptive immune system. More strikingly, systemic inoculation with C1498.CRT cells expressing the model SIYRYYGL (SIY) peptide antigen (C1498.SIY.CRT cells) resulted in almost complete protection from AML development (>90% long term survival vs. 10% of C1498.SIY vector control cells). All animals surviving a primary C1498.SIY.CRT challenge rejected a subsequent re-challenge with C1498.SIY cells, suggesting that CRT-expressing AML cells promote immunologic memory. Significantly enhanced expansion and unregulated IFNγ production were observed among SIY-specific T cell receptor transgenic CD8+ 2C T cells following their adoptive transfer into hosts bearing C1498.SIY.CRT AML cells versus vector control C1498.SIY cells. Interestingly, CRT expression on AML cells did not promote their in vivo phagocytosis by innate immune cells, specifically splenic CD8a+ dendritic cells known to engulf AML cells following their IV inoculation. IL-12 production by CD8α+CD11c+ dendritic cells which had engulfed C1498 and C1498.CRT cells in vivo was similarly induced, and cross-presentation of the SIY antigen to 2C T cells ex vivo by purified CD8a+DCs following in vivo exposure to C1498.SIY or C1498.SIY.CRT cells was also similar. In conclusion, it is clear that expression on CRT on the surface of AML cells leads to robust leukemia-specific T cell activation and expansion resulting in prolonged leukemia-specific survival in AML-bearing animals. Although a direct effect of CRT on innate immune cells, such as dendritic cells, is suspected, the molecular mechanism underlying the “CRT effect” remains unclear, and is being explored further through gene expression analysis in purified DCs which have engulfed CRT-expressing or control AML cells in vivo, as well as in animals genetically deficient in the putative CRT receptor, LRP, in dendritic cells. It will be of interest to analyze spontaneous CRT expression on AML cells from human samples and to correlate cell surface CRT expression with the presence or absence of spontaneous T cell responses to known AML antigens and with clinical outcomes. Disclosures No relevant conflicts of interest to declare.

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 Innate Immunity Mediated Inflammation and Beta Cell Function: Neighbors or Enemies?

2021 ◽  
Vol 11 ◽  
Author(s):  
Antonio Citro ◽  
Francesco Campo ◽  
Erica Dugnani ◽  
Lorenzo Piemonti
Keyword(s):  
T Cells ◽  
Beta Cell ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Active Role ◽  
Pancreatic Tissue ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Beta Cell Destruction

Type 1 diabetes (T1D) is still considered a huge burden because the available treatments are not effective in preventing the onset or progression of the disease. Recently, the idea that diabetes is an autoimmune disease mediated exclusively by T cells has been reshaped. In fact, T cells are not the only players with an active role in beta cell destruction. Macrophages and neutrophils, which physiologically reside in pancreatic tissue, can also participate in tissue homeostasis and damage by promoting innate immune responses and modulating inflammation. During the development of the pancreatic islet inflammation there is a strong interplay of both adaptive and innate immune cells, and the presence of innate immune cells has been demonstrated both in exocrine and endocrine pancreatic compartments during the earliest stages of insulitis. Innate immune cell populations secrete cytokines, which must be considered both as physiological and pathological mediators. In fact, it has been demonstrated that cytokines could regulate directly and indirectly insulin secretion and, simultaneously, trigger inflammatory reaction. Indeed, cytokines pathways could represent targets both to improve glucose metabolism and to prevent autoimmune damage. Concordantly, the combination of immunomodulatory strategies against both innate and adaptive immunity should be tested in the next future, as they can be more efficient to prevent or delay islet damage and T1D onset.

scholarly journals 16 Tumor growth inhibition mediated by a single dose of intratumoral TransCon™ TLR7/8 agonist was associated with activated circulating T and B cells and sustained low levels of systemic cytokines

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A18-A18
Author(s):  
Amer Mirza ◽  
Luis Zuniga ◽  
Karan Uppal ◽  
Kathy Bang ◽  
Enping Hong ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Tumor Growth Inhibition ◽  
Innate Immune Cells ◽  
Tlr Agonists ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Anti Tumor Activity

BackgroundTLR agonists can elicit anti-tumor activity by activating innate immune cells and promoting a proinflammatory microenvironment. Local delivery of TLR agonists has shown encouraging preclinical and clinical anti-tumor activity. However, intratumoral (IT) delivery of naked TLR agonists such as resiquimod, a TLR7/8 agonist, can lead to rapid efflux from the tumor, resulting in acute high systemic drug exposure and transient but high level of peripheral proinflammatory cytokines, thus limiting anti-tumor benefit and increasing risk of cytokine-driven adverse effects.MethodsTransCon™ TLR7/8 Agonist was designed to elicit a sustained and local release of resiquimod following IT administration of a hydrogel depot. In the syngeneic murine CT26 tumor model, a single IT injection of TransCon TLR7/8 Agonist monotherapy was sufficient to induce potent tumor growth inhibition. Following treatment, the induction of key cytokines and chemokines associated with innate immunity was determined.ResultsProinflammatory cytokines (IL-1b, IL-6, and TNFα) were induced following IT TransCon TLR7/8 Agonist treatment, but in contrast to free resiquimod, peak levels were more than 10-fold lower than those observed with an equimolar dose of free resiquimod. The circulating levels of these cytokines were sustained above control alone through Day 21. TH1-associated IFNγ was induced with levels increased at Day 1 and maintained at Day 7. Additionally, expression of myeloid-associated chemokines (KC/GROa/CXCL1, MCP-1/CCL2, IP-10/CXCL10, and MIP-1a/CCL3) were induced and sustained in a largely dose-dependent manner through Day 21. The sustained increase in cytokines was consistent with an increase in circulating innate immune cells, such as NK and myeloid cells. Furthermore, evidence of adaptive immune cell activation was observed as indicated by expression of Ly6C, ICOS and Ki67, which were increased on CD8+ T cells, CD4+ T cells (Ki67, ICOS), and B cells (Ly6C).ConclusionsThese data show that a single IT injection of TransCon TLR7/8 Agonist can elicit sustained expression of key cytokines and chemokines, promote innate immune cell mobilization, activate adaptive immune cells, and mediate robust anti-tumor activity. The levels of the cytokines remained relatively low through the observation period of 21 days, suggesting a low risk of systemic cytokine-associated adverse events. The increase in activated B, T, and NK cells in blood was associated with induction of a potent anti-tumor response, further supporting TransCon TLR7/8 Agonist as a novel and potentially efficacious PRRA therapy. A clinical trial to evaluate its safety and efficacy in cancer patients is currently underway (transcendIT-101; NCT04799054).Ethics ApprovalThe animal studies described were performed in accordance with the ‘Guide for the Care and Use of Laboratory Animals: Eighth Edition’ and approved by the institutional animal care and use committee (IACUC).

scholarly journals Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura

Cephalalgia ◽  
2016 ◽  
Vol 37 (1) ◽  
pp. 36-48 ◽  
Author(s):  
Lisa A McIlvried ◽  
J Agustin Cruz ◽  
Lisa A Borghesi ◽  
Michael S Gold
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Natural Killer T Cells ◽  
Sprague Dawley ◽  
Men And Women ◽  
Sprague Dawley Rats ◽  
Killer T Cells ◽  
Natural Killer T

Aim of investigation Due to compelling evidence in support of links between sex, stress, sympathetic post-ganglionic innervation, dural immune cells, and migraine, our aim was to characterize the impacts of these factors on the type and proportion of immune cells in the dura. Methods Dural immune cells were obtained from naïve or stressed adult male and female Sprague Dawley rats for flow cytometry. Rats with surgical denervation of sympathetic post-ganglionic neurons of the dura were also studied. Results Immune cells comprise ∼17% of all cells in the dura. These included: macrophages/granulocytes (“Macs”; 63.2% of immune cells), dendritic cells (0.88%), T-cells (4.51%), natural killer T-cells (0.51%), natural killer cells (3.08%), and B-cells (20.0%). There were significantly more Macs and fewer B- and natural killer T-cells in the dura of females compared with males. Macs and dendritic cells were significantly increased by stress in males, but not females. In contrast, T-cells were significantly increased in females with a 24-hour delay following stress. Lastly, Macs, dendritic cells, and T-cells were significantly higher in sympathectomized-naïve males, but not females. Conclusions It may not only be possible, but necessary to use different strategies for the most effective treatment of migraine in men and women.

scholarly journals Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

2020 ◽  
Vol 21 (12) ◽  
pp. 4441 ◽  
Author(s):  
Pierpaolo Ginefra ◽  
Girieca Lorusso ◽  
Nicola Vannini
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Cells ◽  
Adoptive Cell Therapy ◽  
Adaptive Immune Response ◽  
Immune Checkpoint Blockade ◽  
Innate Immune ◽  
Innate Immune Cells

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients.

Innate Vα14+natural killer T cells mature dendritic cells, leading to strong adaptive immunity

2007 ◽  
Vol 220 (1) ◽  
pp. 183-198 ◽  
Author(s):  
Shin-Ichiro Fujii ◽  
Kanako Shimizu ◽  
Hiroaki Hemmi ◽  
Ralph M. Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Natural Killer T

scholarly journals Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 456 ◽  
Author(s):  
Philippe Saas ◽  
Alexis Varin ◽  
Sylvain Perruche ◽  
Adam Ceroi
Keyword(s):  
Dendritic Cells ◽  
Lipid Metabolism ◽  
Nuclear Receptors ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Plasmacytoid Dendritic Cell ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Cells ◽  
Immune Functions

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

scholarly journals Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains

2020 ◽  
Vol 8 (2) ◽  
pp. 176 ◽  
Author(s):  
Yann Sellier ◽  
Florence Marliot ◽  
Bettina Bessières ◽  
Julien Stirnemann ◽  
Ferechte Encha-Razavi ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Immune Cells ◽  
Plasma Cells ◽  
Ex Vivo ◽  
Fetal Brain ◽  
Brain Lesions ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Infected Cells

Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage. Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected (n = 13) and moderately affected (n = 8), and 5 were uninfected controls. The respective magnitude of infected cells, immune cells (CD8+, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified by quantitative imaging analysis. Results: Quantities of CD8+, plasma cells, NK cells, macrophages, and HCMV+ cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all p values < 0.05). A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis. Conclusions: The higher expression of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells. These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions. The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis.

Sign in / Sign up

Export Citation Format

Share Document