scholarly journals PPARγand the Innate Immune System Mediate the Resolution of Inflammation

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Amanda Croasdell ◽  
Parker F. Duffney ◽  
Nina Kim ◽  
Shannon H. Lacy ◽  
Patricia J. Sime ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
M2 Macrophage ◽  
Resolution Of Inflammation ◽  
Anti Inflammatory

The resolution of inflammation is an active and dynamic process, mediated in large part by the innate immune system. Resolution represents not only an increase in anti-inflammatory actions, but also a paradigm shift in immune cell function to restore homeostasis. PPARγ, a ligand activated transcription factor, has long been studied for its anti-inflammatory actions, but an emerging body of literature is investigating the role of PPARγand its ligands (including thiazolidinediones, prostaglandins, and oleanolic acids) in all phases of resolution. PPARγcan shift production from pro- to anti-inflammatory mediators by neutrophils, platelets, and macrophages. PPARγand its ligands further modulate platelet and neutrophil function, decreasing trafficking, promoting neutrophil apoptosis, and preventing platelet-leukocyte interactions. PPARγalters macrophage trafficking, increases efferocytosis and phagocytosis, and promotes alternative M2 macrophage activation. There are also roles for this receptor in the adaptive immune response, particularly regarding B cells. These effects contribute towards the attenuation of multiple disease states, including COPD, colitis, Alzheimer’s disease, and obesity in animal models. Finally, novel specialized proresolving mediators—eicosanoids with critical roles in resolution—may act through PPARγmodulation to promote resolution, providing another exciting area of therapeutic potential for this receptor.

scholarly journals Adaptive and innate immune cell responses in tendons and lymph nodes after tendon injury and repair

2020 ◽  
Vol 128 (3) ◽  
pp. 473-482 ◽  
Author(s):  
Andrew C. Noah ◽  
Thomas M. Li ◽  
Leandro M. Martinez ◽  
Susumu Wada ◽  
Jacob B. Swanson ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Immune System ◽  
Innate Immune System ◽  
Immune Cell ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Innate Immune ◽  
Adaptive Immune ◽  
Immune Cell Response

Tendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate immune system, such as neutrophils and macrophages, have been studied in tendon injuries. However, the adaptive immune system, comprising specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues, but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we determined how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month-old male mice. We observed that lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons, and that the lymphatics drain into the popliteal lymph node. We then created an acute Achilles tenotomy followed by repair, and collected tendons and popliteal lymph nodes 1, 2, and 4 wk after injury. Tendon injury resulted in a robust adaptive immune cell response that followed an initial innate immune cell response in tendons and lymph nodes. Monocytes, neutrophils, and macrophages initially accumulated at 1 wk after injury in tendons, while dendritic cells and CD4+ T cells peaked at 2 wk after injury. B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury, and adaptive immune cells may play a role in regulating tendon healing. NEW & NOTEWORTHY While the innate immune system, consisting of macrophages and related hematopoietic cells, has been studied in tendon injury, less is known about the adaptive immune system. Using a mouse model of Achilles tendon tenotomy and repair, we observed an adaptive immune cell response, consisting of CD4+ and CD8+ T cells, and B cells, which occur through 4 wk after tendon injury. This response appeared to be coordinated by the draining popliteal lymph node.

scholarly journals Insights into Innate Immune Response Against SARS-CoV-2 Infection

2021 ◽  
Vol 29 (3) ◽  
pp. 255-269
Author(s):  
Adina Huțanu ◽  
Anca Meda Georgescu ◽  
Akos Vince Andrejkovits ◽  
William Au ◽  
Minodora Dobreanu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Innate Immune System ◽  
Time Course ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Response ◽  
Humoral Factors ◽  
Key Steps

Abstract The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

scholarly journals SARS-CoV-2 and interferon blockade

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Betty Diamond ◽  
Bruce T. Volpe ◽  
Sonya VanPatten ◽  
Yousef Al Abed
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Neutralizing Antibodies ◽  
Cytotoxic T Cells ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Production ◽  
Therapeutic Implications ◽  
Adaptive Immune

Abstract The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.

scholarly journals Orchestration of Adaptive T Cell Responses by Neutrophil Granule Contents

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Danielle Minns ◽  
Katie Jane Smith ◽  
Emily Gwyer Findlay
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Innate Immune System ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Cell Immunity

Neutrophils are the most abundant leukocytes in peripheral blood and respond rapidly to danger, infiltrating tissues within minutes of infectious or sterile injury. Neutrophils were long thought of as simple killers, but now we recognise them as responsive cells able to adapt to inflammation and orchestrate subsequent events with some sophistication. Here, we discuss how these rapid responders release mediators which influence later adaptive T cell immunity through influences on DC priming and directly on the T cells themselves. We consider how the release of granule contents by neutrophils—through NETosis or degranulation—is one way in which the innate immune system directs the phenotype of the adaptive immune response.

Innate Immunity Is Responsible for Early Allorejection of Donor Bone Marrow Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3523-3523
Author(s):  
Hong Xu ◽  
Jun Yan ◽  
Ziqiang Zhu ◽  
Lala-Rukh Hussain ◽  
Yiming Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Innate Immunity ◽  
Immune System ◽  
T Cell ◽  
Innate Immune System ◽  
Immune Cell ◽  
Marrow Cell ◽  
Donor Cell ◽  
Innate Immune ◽  
Kinetics Of

Abstract Abstract 3523 Poster Board III-460 Adaptive immunity, especially T cells, has long been believed to be the dominant immune response in allogeneic transplantation. However, innate immunity has been recently shown to pose a significant barrier to the induction of tolerance to solid organ transplants. The role of the innate immune system in bone marrow cell alloreactivity has not been addressed. The innate immune system provides the first line of defense in the removal of pathogens because of the delay in generation of adaptive immune responses. Our present findings show that innate immunity is a significant first line barrier in bone marrow cell (BMC) rejection. To determine the effect of innate immune cell populations on rejection of donor BMCs, T cell deficient mice (TCR β/δ−/−) were used as BMC recipients in in vivo cytotoxicity assays (Figure A). TCRβ/δ−/− mice have normal innate immune cell populations but do not initiate adaptive cell-mediated cytotoxic or humoral responses. 20 × 106 CFSE labeled donor (high CFSE fluorescence intensity) and recipient control splenocytes (low CFSE fluorescence intensity) were injected into TCRβ/δ−/− and wildtype control B6 recipient mice. Donor cell survival was compared over time. Donor BALB/c splenocytes were eliminated in wildtype B6, with rejection complete by day 3. The kinetics of elimination of donor cells in TCRβ/δ−/− mice was similar to that for wildtype B6 controls, with donor cells eliminated by day 3. These results indicate that early rejection of the splenocytes in wildtype mice was T cell-independent. The acute rejection of BMC in wildtype B6 recipients occurred within 3 days, which is prior to the time required for T cell activation. Thus the effectors mediating BMC rejection would be the innate immune cells: macrophages, neutrophils, or NK cells. To rule out potential involvement of natural Abs in the cytotoxicity we observed in the TCRβ/δ−/− mice, Rag−/− mice were used as recipients (Figure B). Rag−/− mice do not produce mature T cells or B cells. 20 × 106 CFSE labeled donor (high CFSE intensity) and recipient control BM cells (low CFSE intensity) were injected into Rag−/−mice. Rag−/− and wildtype B6 control mice exhibited similar kinetics of donor cell cytolysis. The rapid elimination of allogeneic cells from immunocompetent mice is comparable with that observed in T cell- (TCRβ/δ−/−) or T and B cell- (Rag−/−) deficient mice indicates that allogeneic cells are subject to T cell-independent rejection at the early time period after cell infusion (≤ 3 days). As the kinetics of cytotoxicity were similar in experiments using either splenocytes or BMCs as target cells in our later experiments, our data suggest that the innate immune system is responsible for early allorejection of donor BMC at the early inductive period for adaptive immunity. These findings may have significant impact on the development of immune-based nonmyeloablative conditioning strategies and show for the first time that a dominant factor in BMC rejection is contributed by innate immune responses. Disclosures: Bozulic: Regenerex: Employment. Ildstad:Regenerex: Equity Ownership.

scholarly journals Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
A. J. Theron ◽  
H. C. Steel ◽  
G. R. Tintinger ◽  
C. M. Gravett ◽  
R. Anderson ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Cell Types ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Cysteinyl Leukotriene ◽  
Anti Inflammatory ◽  
Cysteinyl Leukotriene Receptor ◽  
Underlying Mechanisms

Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8+cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5′-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophilsin vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.

The older brain, inflammation, vaccination and the prevention of dementia

2010 ◽  
Vol 20 (4) ◽  
pp. 288-308
Author(s):  
JW Neal
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Transgenic Animal ◽  
Innate Immune ◽  
Brain Inflammation ◽  
Amyloid Peptide ◽  
System Response ◽  
Protective Function

SummaryAn important protective function of the brain's innate immune system is to detect the presence of proteins such as amyloid and to remove them before they become neurotoxic, as is thought to occur in Alzheimer's disease (AD). Ageing affects the immune system response to infection and can influence the systemic response to vaccination and other potential immunotherapeutic agents. The generation of systemic antibodies is a vital component of the immune response, facilitating the identification and clearance of pathogens from the central nervous system (CNS). Experimental evidence using transgenic animal models of AD has shown successful clearance of amyloid from the CNS following vaccination with an amyloid peptide, and consequently a trial of amyloid beta peptide (Aβ) vaccination was undertaken in older people with AD. This produced some unexpected results, as not only was there evidence for amyloid plaque removal, but also a small number of cases developed encephalitis. A detailed review of the response to vaccination and the neuropathology findings are discussed, showing that the findings are understandable given the effects of ageing upon the innate immune system in the brain. Finally, the therapeutic potential of manipulating the regulatory components of the ageing innate immune system in order to inhibit brain inflammation and reduce cognitive decline is outlined.

Bacopamonnieri (L.) exerts anti-inflammatory effects on cells of the innate immune system in vitro

2014 ◽  
Vol 5 (3) ◽  
pp. 517-520 ◽  
Author(s):  
Roderick Williams ◽  
Gerald Münch ◽  
Erika Gyengesi ◽  
Louise Bennett
Keyword(s):  
Immune System ◽  
Acute Pain ◽  
Innate Immune System ◽  
Selective Inhibition ◽  
Innate Immune ◽  
Inflammatory Activity ◽  
Consequent Reduction ◽  
Cox 2 ◽  
Anti Inflammatory

Bacopa monnieri(L., BM) is a traditional Ayurvedic medicinal herb recognised for its efficacy in relieving acute pain and inflammation, as related to selective inhibition of cyclo-oxygenase-2 (COX-2) enzyme and consequent reduction in COX-2-mediated prostanoid mediators. Anti-inflammatory activity of BM might also account for its benefits in cognition.

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