scholarly journals IgA potentiates NETosis in response to viral infection

2021 ◽  
Vol 118 (27) ◽  
pp. e2101497118
Author(s):  
Hannah D. Stacey ◽  
Diana Golubeva ◽  
Alyssa Posca ◽  
Jann C. Ang ◽  
Kyle E. Novakowski ◽  
...  
Keyword(s):  
Viral Infections ◽  
Immune Effector ◽  
Effector Cells ◽  
Cell Death Pathway ◽  
Mucosal Surfaces ◽  
Immune Effector Cells ◽  
Antiviral Function ◽  
Nadph Oxidase Complex ◽  
Alpha Receptors ◽  
Mucosal Pathogens

IgA is the second most abundant antibody present in circulation and is enriched at mucosal surfaces. As such, IgA plays a key role in protection against a variety of mucosal pathogens including viruses. In addition to neutralizing viruses directly, IgA can also stimulate Fc-dependent effector functions via engagement of Fc alpha receptors (Fc-αRI) expressed on the surface of certain immune effector cells. Neutrophils are the most abundant leukocyte, express Fc-αRI, and are often the first to respond to sites of injury and infection. Here, we describe a function for IgA–virus immune complexes (ICs) during viral infections. We show that IgA–virus ICs potentiate NETosis—the programmed cell-death pathway through which neutrophils release neutrophil extracellular traps (NETs). Mechanistically, IgA–virus ICs potentiated a suicidal NETosis pathway via engagement of Fc-αRI on neutrophils through a toll-like receptor–independent, NADPH oxidase complex–dependent pathway. NETs also were capable of trapping and inactivating viruses, consistent with an antiviral function.

scholarly journals IgA Potentiates NETosis in Response to Viral Infection

2021 ◽  
Author(s):  
Hannah D. Stacey ◽  
Diana Golubeva ◽  
Alyssa Posca ◽  
Jann C. Ang ◽  
Kyle E. Novakowski ◽  
...  
Keyword(s):  
Viral Infections ◽  
Immune Effector ◽  
Effector Cells ◽  
Cell Death Pathway ◽  
Mucosal Surfaces ◽  
Immune Effector Cells ◽  
Antiviral Function ◽  
Nadph Oxidase Complex ◽  
Alpha Receptors ◽  
Mucosal Pathogens

ABSTRACTIgA is the second most abundant antibody present in circulation and is enriched at mucosal surfaces. As such, IgA plays a key role in protection against a variety of mucosal pathogens, including viruses. In addition to neutralizing viruses directly, IgA can also stimulate Fc-dependent effector functions via engagement of Fc alpha receptors (FcαRI) expressed on the surface of certain immune effector cells. Neutrophils are the most abundant leukocyte, express FcαRI, and are often the first to respond to sites of injury and infection. Here, we describe a novel function for IgA:virus immune complexes (ICs) during viral infections. We show that IgA:virus ICs potentiate NETosis – the programmed cell death pathway through which neutrophils release neutrophil extracellular traps (NETs). Mechanistically, IgA:virus ICs potentiated a suicidal NETosis pathway via engagement of FcαRI on neutrophils through a toll-like receptor (TLR)-independent, NADPH oxidase complex-dependent pathway. NETs also were capable of trapping and inactivating viruses, consistent with an antiviral function.

scholarly journals Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Fabio Morandi ◽  
Roberta Rizzo ◽  
Enrico Fainardi ◽  
Nathalie Rouas-Freiss ◽  
Vito Pistoia
Keyword(s):  
Immune Response ◽  
Viral Infections ◽  
De Novo ◽  
Inflammatory Diseases ◽  
Wide Spectrum ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
Hematological Tumors

HLA-G is a HLA-class Ib molecule with potent immunomodulatory activities, which is expressed in physiological conditions, where modulation of the immune response is required to avoid allograft recognition (i.e., maternal-fetal interface or transplanted patients). However, HLA-G can be expressedde novoat high levels in several pathological conditions, including solid and hematological tumors and during microbial or viral infections, leading to the impairment of the immune response against tumor cells or pathogens, respectively. On the other hand, the loss of HLA-G mediated control of the immune responses may lead to the onset of autoimmune/inflammatory diseases, caused by an uncontrolled activation of the immune effector cells. Here, we have reviewed novel findings on HLA-G functions in different physiological and pathological settings, which have been published in the last two years. These studies further confirmed the important role of this molecule in the modulation of the immune system.

The Role of Microglia in Sporadic Alzheimer’s Disease

2021 ◽  
Vol 79 (3) ◽  
pp. 961-968
Author(s):  
Wolfgang J. Streit ◽  
Habibeh Khoshbouei ◽  
Ingo Bechmann
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Genetic Mutations ◽  
Sporadic Alzheimer’S Disease ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
Amyloid Cascade

Microglia constitute the brain’s immune system and their involvement in Alzheimer’s disease has been discussed. Commonly, and in line with the amyloid/neuroinflammation cascade hypothesis, microglia have been portrayed as potentially dangerous immune effector cells thought to be overactivated by amyloid and producing neurotoxic inflammatory mediators that lead to neurofibrillary degeneration. We disagree with this theory and offer as an alternative the microglial dysfunction theory stating that microglia become impaired in their normally neuroprotective roles because of aging, i.e., they become senescent and aging neurons degenerate because they lack the needed microglial support for their survival. Thus, while the amyloid cascade theory relies primarily on genetic data, the dysfunction theory incorporates aging as a critical etiological factor. Aging is the greatest risk factor for the sporadic (late-onset) and most common form of Alzheimer’s disease, where fully penetrant genetic mutations are absent. In this review, we lay out and discuss the human evidence that supports senescent microglial dysfunction and conflicts with the amyloid/neuroinflammation idea.

scholarly journals Next-generation cell therapies: the emerging role of CAR-NK cells

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 570-578
Author(s):  
Rafet Basar ◽  
May Daher ◽  
Katayoun Rezvani
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Natural Killer ◽  
Γδ T Cells ◽  
Antigen Receptors ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells

Abstract T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed the paradigm of treatment for many patients with relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T cell therapy in both the autologous and allogeneic settings, including practical, logistical, and toxicity issues. Given these concerns, there is a rapidly growing interest in natural killer cells as alternative vehicles for CAR engineering, given their unique biological features and their established safety profile in the allogeneic setting. Other immune effector cells, such as invariant natural killer T cells, γδ T cells, and macrophages, are attracting interest as well and eventually may be added to the repertoire of engineered cell therapies against cancer. The pace of these developments will undoubtedly benefit from multiple innovative technologies, such as the CRISPR-Cas gene editing system, which offers great potential to enhance the natural ability of immune effector cells to eliminate refractory cancers.

Soluble CD70: a novel immunotherapeutic agent for experimental glioblastoma

2010 ◽  
Vol 113 (2) ◽  
pp. 280-285 ◽  
Author(s):  
James Miller ◽  
Guenter Eisele ◽  
Ghazaleh Tabatabai ◽  
Steffen Aulwurm ◽  
Gabriele von Kürthy ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Malignant Gliomas ◽  
Ectopic Expression ◽  
Glioma Cells ◽  
Interferon Γ ◽  
Soluble Form ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells

Object Given the overall poor outcome with current treatment strategies in malignant gliomas, immunotherapy has been considered a promising experimental approach to glioblastoma for more than 2 decades. A cell surface molecule, CD70, may induce potent antitumor immune responses via activation of the costimulatory receptor CD27 expressed on immune effector cells. There is evidence that a soluble form of CD70 (sCD70) may exhibit biological activity, too. A soluble costimulatory ligand is attractive because it may facilitate immune activation and may achieve a superior tissue distribution. Methods To test the antiglioma effect of sCD70, the authors genetically modified SMA-560 mouse glioma cells to secrete the extracellular domain of CD70. They assessed the immunogenicity of the transfected cells in cocultures with immune effector cells by the determination of immune cell proliferation and the release of interferon-γ. Syngeneic VM/Dk mice were implanted orthotopically with control or sCD70-releasing glioma cells to determine a survival benefit mediated by sCD70. Depletion studies were performed to identify the cellular mediators of prolonged survival of sCD70-releasing glioma-bearing mice. Results The authors found that ectopic expression of sCD70 enhanced the proliferation and interferon-γ release of syngeneic splenocytes in vitro. More importantly, sCD70 prolonged the survival of syngeneic VM/Dk mice bearing intracranial SMA-560 gliomas. The survival rate at 60 days increased from 5 to 45%. Antibody-mediated depletion of CD8-positive T cells abrogates the survival advantage conferred by sCD70. Conclusions These data suggest that sCD70 is a potent stimulator of antiglioma immune responses that depend critically on CD8-positive T cells. Soluble CD70 could be a powerful adjuvant for future immunotherapy trials for glioblastoma.

scholarly journals Antibody-based therapy of leukaemia

2009 ◽  
Vol 11 ◽  
Author(s):  
John C. Morris ◽  
Thomas A. Waldmann
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cell ◽  
Gemtuzumab Ozogamicin ◽  
Cell Leukaemia ◽  
Target Cells ◽  
Immune Effector ◽  
Effector Cells ◽  
Prolymphocytic Leukaemia ◽  
Immune Effector Cells

Over the past decade, monoclonal antibodies have dramatically impacted the treatment of haematological malignancies, as evidenced by the effect of rituximab on the response rate and survival of patients with follicular and diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal antibodies – the anti-CD33 immunotoxin gemtuzumab ozogamicin and the CD52-directed antibody alemtuzumab – are approved for treatment of relapsed acute myeloid leukaemia in older patients and B cell chronic lymphocytic leukaemia, respectively. Although not approved for such treatment, alemtuzumab is also active against T cell prolymphocytic leukaemia, cutaneous T cell lymphoma and Sézary syndrome, and adult T cell leukaemia and lymphoma. In addition, rituximab has demonstrated activity against B cell chronic lymphocytic and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22, CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the treatment of leukaemia. Here, we discuss how these new antibodies have been engineered to reduce immunogenicity and improve antibody targeting and binding. Improved interactions with Fc receptors on immune effector cells can enhance destruction of target cells through antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells.

The interactions between major immune effector cells and Hepatocellular Carcinoma: A systematic review

2021 ◽  
Vol 101 ◽  
pp. 108220
Author(s):  
Markus Bo Schoenberg ◽  
Xiaokang Li ◽  
Xinyu Li ◽  
Yongsheng Han ◽  
Nikolaus Börner ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells

scholarly journals Transcriptomic Correlates of Immunologic Activation in Head and Neck and Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Cristina Saiz-Ladera ◽  
Mariona Baliu-Piqué ◽  
Francisco J. Cimas ◽  
Aránzazu Manzano ◽  
Vanesa García-Barberán ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Immune System ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Effector ◽  
Effector Cells ◽  
Favorable Prognosis ◽  
Immune Effector Cells ◽  
Tumor Types

Targeting the immune system has emerged as an effective therapeutic strategy for the treatment of various tumor types, including Head and Neck Squamous Cell Carcinoma (HNSCC) and Non-small-Cell Lung Cancer (NSCLC), and checkpoint inhibitors have shown to improve patient survival in these tumor types. Unfortunately, not all cancers respond to these agents, making it necessary to identify responsive tumors. Several biomarkers of response have been described and clinically tested. As of yet what seems to be clear is that a pre-activation state of the immune system is necessary for these agents to be efficient. In this study, using established transcriptomic signatures, we identified a group of gene combination associated with favorable outcome in HNSCC linked to a higher presence of immune effector cells. CD2, CD3D, CD3E, and CXCR6 combined gene expression is associated with improved outcome of HNSCC patients and an increase of infiltrating immune effector cells. This new signature also identifies a subset of cervical squamous cell carcinoma (CSCC) patients with favorable prognosis, who show an increased presence of immune effector cells in the tumor, which outcome shows similarities with the HP-positive HNSCC cohort of patients. In addition, CD2, CD3D, CD3E, and CXCR6 signature is able to predict the best favorable prognosis in terms of overall survival of CSSC patients. Of note, these findings were not reproduced in other squamous cell carcinomas like esophageal SCC or lung SCC. Prospective confirmatory studies should be employed to validate these findings.

Pilot Trial of Interleukin-2 With Granulocyte Colony-Stimulating Factor for the Mobilization of Progenitor Cells in Advanced Breast Cancer Patients Undergoing High-Dose Chemotherapy: Expansion of Immune Effectors Within the Stem-Cell Graft and Post–Stem-Cell Infusion

2001 ◽  
Vol 19 (3) ◽  
pp. 634-644 ◽  
Author(s):  
J.A. Sosman ◽  
P. Stiff ◽  
S.M. Moss ◽  
P. Sorokin ◽  
B. Martone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Interleukin 2 ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
Stem Cell Graft

PURPOSE: To evaluate whether administration of interleukin-2 (IL-2) with granulocyte colony-stimulating factor (G-CSF) improves mobilization of immune effector cells into the stem-cell graft of patients undergoing high-dose chemotherapy and autografting. PATIENTS AND METHODS: We performed a trial of stem-cell mobilization with IL-2 and G-CSF in advanced breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin and stem cells followed by IL-2. The trial defined immune, hematologic, and clinical effects of IL-2 in this setting. RESULTS: Of 32 patients enrolled, nine received G-CSF alone for mobilization. Twenty-one of 23 patients mobilized with IL-2 plus G-CSF had stem cells collected with more mononuclear cells than those receiving G-CSF (19.3 v 10.4 × 108/kg; P = .006), but fewer CD34+ progenitor cells (6.9 v 22.0 × 106/kg; P = .049). The IL-2 plus G-CSF–mobilized patients had greater numbers of activated T (CD3+/CD25+) cells (P = .009), natural killer (NK; CD56+) cells (P = .007), and activated NK (CD56 bright+) cells (P = .039) than those patients mobilized with G-CSF. NK (P = .042) and lymphokine-activated killer (LAK) (P = .016) activity was increased in those mobilized with IL-2 + G-CSF, whereas G-CSF–mobilized patients had a decline in cytolytic activity. In the third week posttransplantation, immune reconstitution was superior in those mobilized with IL-2 plus G-CSF based on greater numbers of activated T cells (P = .003), activated NK cells (P = .04), and greater LAK activity (P = .003). The 16 of 21 IL-2 + G-CSF–mobilized patients with adequate numbers of stem cells (> 1.5 × 106 CD34+ cells/kg) collected engrafted rapidly posttransplantation. CONCLUSION: The results demonstrate that G-CSF + IL-2 can enhance the number and function of antitumor effector cells in a mobilized autograft without impairing the hematologic engraftment, provided that CD34 cell counts are more than 1.5 × 106 cells/kg. Mobilization of CD34+ stem cells does seem to be adversely affected. In those mobilized with IL-2 and G-CSF, post–stem-cell immune reconstitution of antitumor immune effector cells was enhanced.

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