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.

The role of natural killer cells, gamma delta T-cells and other innate immune cells in spondyloarthritis

2013 ◽  
Vol 25 (4) ◽  
pp. 434-439 ◽  
Author(s):  
Mohammad H. Al-Mossawi ◽  
Anna Ridley ◽  
Sarah Kiedel ◽  
Paul Bowness
Keyword(s):  
T Cells ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Innate Immune ◽  
Gamma Delta T Cells ◽  
Innate Immune Cells ◽  
Gamma Delta ◽  
Killer Cells

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 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.

Immunology and cytokine pathways

2018 ◽  
Author(s):  
Bruce Kirkham
Keyword(s):  
Psoriatic Arthritis ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
New Information ◽  
Key Pathways

Psoriatic arthritis immunopathology has become the subject of intense study. These findings show differences to other forms of inflammatory arthritis in key pathways. Increased knowledge of innate immunity and the important role of IL-17/23 biology in both psoriasis and psoriatic arthritis, have led to new theories of immunopathogenesis in both conditions. Direct environmental stimuli could trigger innate immune cells resident in skin, which may then initiate a chronic adaptive immune response. The joint has fewer resident innate immune cells, but new studies show cells producing IL-17 may play key roles in immunopathology. The new information summarized here will provide important hypotheses for investigation of pathogenic pathways. Differences in non-immune cell function may also be critical mediators of response, for example, production of IL-12 or IL-23 by dendritic cells. Keratinocytes in skin and fibroblasts in joints may be critical in mediating cytokine production and effector function.

scholarly journals Contribution ofIn Vivoand Organotypic 3D Models to Understanding the Role of Macrophages and Neutrophils in the Pathogenesis of Psoriasis

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Isabelle Lorthois ◽  
Daniel Asselineau ◽  
Nathalie Seyler ◽  
Roxane Pouliot
Keyword(s):  
Immune Cells ◽  
Skin Disease ◽  
Immune Cell ◽  
3D Models ◽  
Current Data ◽  
Innate Immune ◽  
Innate Immune Cells

Psoriasis, a common chronic immune-mediated skin disease, is histologically characterized by a rapid keratinocyte turnover and differentiation defects. Key insights favor the idea that T cells are not the only key actors involved in the inflammatory process. Innate immune cells, more precisely neutrophils and macrophages, provide specific signals involved in the initiation and the maintenance of the pathogenesis. Current data from animal models and, to a lesser extent, three-dimensionalin vitromodels have confirmed the interest in leaning towards other immune cell types as a potential new cellular target for the treatment of the disease. Although these models do not mimic the complex phenotype nor all human features of psoriasis, their development is necessary and essential to better understand reciprocal interactions between skin cells and innate immune cells and to emphasize the crucial importance of the local lesional microenvironment. In this review, through the use ofin vivoand 3D organotypic models, we aim to shed light on the crosstalk between epithelial and immune components and to discuss the role of secreted inflammatory molecules in the development of this chronic skin disease.

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 The Role of Innate Immune Cells in Tumor Invasion and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5885
Author(s):  
Yu-Kuan Huang ◽  
Rita A. Busuttil ◽  
Alex Boussioutas
Keyword(s):  
Tumor Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Tumor Invasion ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Invasion And Metastasis ◽  
Immune Therapies

Metastasis is considered one of the hallmarks of cancer and enhanced tumor invasion and metastasis is significantly associated with cancer mortality. Metastasis occurs via a series of integrated processes involving tumor cells and the tumor microenvironment. The innate immune components of the microenvironment have been shown to engage with tumor cells and not only regulate their proliferation and survival, but also modulate the surrounding environment to enable cancer progression. In the era of immune therapies, it is critical to understand how different innate immune cell populations are involved in this process. This review summarizes recent literature describing the roles of innate immune cells during the tumor metastatic cascade.

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.

scholarly journals The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Low Dose ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Atp Production ◽  
Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

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