scholarly journals Mucorales Species and Macrophages

2020 ◽  
Vol 6 (2) ◽  
pp. 94 ◽  
Author(s):  
Francisco E. Nicolás ◽  
Laura Murcia ◽  
Eusebio Navarro ◽  
María Isabel Navarro-Mendoza ◽  
Carlos Pérez-Arques ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Genetic Manipulation ◽  
Mucor Circinelloides ◽  
Rnai Pathway ◽  
Invasion Pathways ◽  
Immune Effector ◽  
Effector Cells ◽  
Regulatory Pathways ◽  
Species Specific ◽  
Key Aspects

Mucormycosis is an emerging fungal infection caused by Mucorales with an unacceptable high mortality rate. Mucorales is a complex fungal group, including eleven different genera that can infect humans. This heterogeneity is associated with species-specific invasion pathways and responses to the host defense mechanisms. The host innate immune system plays a major role in preventing Mucorales growth and host invasion. In this system, macrophages are the main immune effector cells in controlling these fungi by rapid and efficient phagocytosis of the spores. However, Mucorales have evolved mechanisms to block phagosomal maturation and species-specific mechanisms to either survive as dormant spores inside the macrophage, as Rhizopus species, or geminate and escape, as Mucor species. Classical fungal models of mucormycosis, mostly Rhizopus, have made important contributions to elucidate key aspects of the interaction between Mucorales and macrophages, but they lack robust tools for genetic manipulation. The recent introduction of the genetically tractable Mucor circinelloides as a model of mucormycosis offers the possibility to analyze gene function. This has allowed the identification of regulatory pathways that control the fungal response to phagocytosis, including a non-canonical RNAi pathway (NCRIP) that regulates the expression of most genes regulated by phagocytosis.

scholarly journals Immunological Aspects ofCandidaandAspergillusSystemic Fungal Infections

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Christoph Mueller-Loebnitz ◽  
Helmut Ostermann ◽  
Anke Franzke ◽  
Juergen Loeffler ◽  
Lutz Uharek ◽  
...  
Keyword(s):  
High Risk ◽  
Defense Mechanisms ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Immunosuppressive Drugs ◽  
Immune Defense ◽  
Immunological Mechanism ◽  
Immune Effector ◽  
Effector Cells ◽  
Risk Patients

Patients with allogeneic stem cell transplantation (SCT) have a high risk of invasive fungal infections (IFIs) even after neutrophil regeneration. Immunological aspects might play a very important role in the IFI development in these patients. Some data are available supporting the identification of high-risk patients with IFI for example patients receiving stem cells from TLR4 haplotype S4 positive donors. Key defense mechanisms against IFI include the activation of neutrophils, the phagocytosis of germinating conidia by dendritic cells, and the fight of the cells of the innate immunity such as monocytes and natural killer cells against germlings and hyphae. Furthermore, immunosuppressive drugs interact with immune effector cells influencing the specific fungal immune defense and antimycotic drugs might interact with immune response. Based on the current knowledge on immunological mechanism inAspergillus fumigatus, the first approaches of an immunotherapy using human T cells are in development. This might be an option for the future of aspergillosis patients having a poor prognosis with conventional treatment.

scholarly journals Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

2021 ◽  
Vol 22 (9) ◽  
pp. 4589
Author(s):  
Martin Voss ◽  
Johanna Kotrba ◽  
Evelyn Gaffal ◽  
Konstantinos Katsoulis-Dimitriou ◽  
Anne Dudeck
Keyword(s):  
Mast Cells ◽  
Defense Mechanisms ◽  
Secretory Granules ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Disease Exacerbation ◽  
Immune Effector ◽  
Effector Cells ◽  
Proinflammatory Mediators ◽  
Chronic Skin

Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

scholarly journals Axotrophin and leukaemia inhibitory factor (LIF) in transplantation tolerance

2005 ◽  
Vol 360 (1461) ◽  
pp. 1687-1694 ◽  
Author(s):  
Su M Metcalfe
Keyword(s):  
Stem Cells ◽  
Treg Cells ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Transplantation Tolerance ◽  
Immune Effector ◽  
Effector Cells ◽  
Regulatory Pathways ◽  
Draining Lymph Node

Immune self-tolerance is controlled by a subset of T lymphocytes that are regulatory (Treg) and epigenetically programmed to suppress auto-reactive immune effector cells in vivo . By extrapolation, donor-specific transplantation tolerance might be controlled by donor-specific Treg that have acquired the appropriate epigenetic program for tolerance. Although such tolerance has yet to be achieved in man, proof of concept comes from mouse models where regulatory transplantation tolerance can be induced within the complex micro-environment of the spleen or draining lymph node. By studying whole spleen cell populations in a murine model of transplantation tolerance we have incorporated a complexity of environmental factors when looking for specific features that characterize tolerance versus aggression. This approach has revealed unexpected patterns of gene activity in tolerance and most notably that a novel stem cell gene, axotrophin , regulates T lymphocyte responsiveness both in terms of proliferation and in release of leukaemia inhibitory factor (LIF). Since LIF is a regulator of stem cells in addition to being a key neuropoietic cytokine, these preliminary results linking both axotrophin and LIF to transplantation tolerance lead us to propose that regulatory pathways encoded during the epigenetic development of Treg cells are related to pathways that regulate fate determination of stem cells.

scholarly journals Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

2021 ◽  
Author(s):  
Martin Voss ◽  
Johanna Kotrba ◽  
Evelyn Gaffal ◽  
Konstantinos Katsoulis-Dimitriou ◽  
Anne Dudeck
Keyword(s):  
Mast Cells ◽  
Defense Mechanisms ◽  
Secretory Granules ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Disease Exacerbation ◽  
Immune Effector ◽  
Effector Cells ◽  
Life Threatening ◽  
Chronic Skin

Mast cells (MCs) are best known as key effector cells of immediate type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first line defense against pathogens. Their main characteristic, the huge amount of preformed pro-inflammatory mediators embedded in secretory granules, allow for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases, but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs all the way from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

scholarly journals Environmental RNAi pathways in the two-spotted spider mite

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mosharrof Mondal ◽  
Jacob Peter ◽  
Obrie Scarbrough ◽  
Alex Flynt
Keyword(s):  
Gene Expression ◽  
Small Rna ◽  
Spider Mite ◽  
Genetic Manipulation ◽  
Model Organisms ◽  
Rnai Pathway ◽  
Plant Host ◽  
Rnai Technology ◽  
Two Spotted Spider Mite ◽  
Multicellular Organisms

Abstract Background RNA interference (RNAi) regulates gene expression in most multicellular organisms through binding of small RNA effectors to target transcripts. Exploiting this process is a popular strategy for genetic manipulation and has applications that includes arthropod pest control. RNAi technologies are dependent on delivery method with the most convenient likely being feeding, which is effective in some animals while others are insensitive. The two-spotted spider mite, Tetranychus urticae, is prime candidate for developing RNAi approaches due to frequent occurrence of conventional pesticide resistance. Using a sequencing-based approach, the fate of ingested RNAs was explored to identify features and conditions that affect small RNA biogenesis from external sources to better inform RNAi design. Results Biochemical and sequencing approaches in conjunction with extensive computational assessment were used to evaluate metabolism of ingested RNAs in T. urticae. This chelicerae arthropod shows only modest response to oral RNAi and has biogenesis pathways distinct from model organisms. Processing of synthetic and plant host RNAs ingested during feeding were evaluated to identify active substrates for spider mite RNAi pathways. Through cataloging characteristics of biochemically purified RNA from these sources, trans-acting small RNAs could be distinguished from degradation fragments and their origins documented. Conclusions Using a strategy that delineates small RNA processing, we found many transcripts have the potential to enter spider mite RNAi pathways, however, trans-acting RNAs appear very unstable and rare. This suggests potential RNAi pathway substrates from ingested materials are mostly degraded and infrequently converted into regulators of gene expression. Spider mites infest a variety of plants, and it would be maladaptive to generate diverse gene regulators from dietary RNAs. This study provides a framework for assessing RNAi technology in organisms where genetic and biochemical tools are absent and benefit rationale design of RNAi triggers for T.urticae.

scholarly journals Targeting HIF-1 alpha transcriptional activity drives cytotoxic immune effector cells into melanoma and improves combination immunotherapy

Oncogene ◽  
2021 ◽  
Author(s):  
Audrey Lequeux ◽  
Muhammad Zaeem Noman ◽  
Malina Xiao ◽  
Kris Van Moer ◽  
Meriem Hasmim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Transcriptional Activity ◽  
Immune Cell ◽  
Tumor Resistance ◽  
Combination Strategy ◽  
Immune Effector ◽  
Effector Cells ◽  
Melanoma Patients ◽  
The Impact

AbstractHypoxia is a key factor responsible for the failure of therapeutic response in most solid tumors and promotes the acquisition of tumor resistance to various antitumor immune effectors. Reshaping the hypoxic immune suppressive tumor microenvironment to improve cancer immunotherapy is still a relevant challenge. We investigated the impact of inhibiting HIF-1α transcriptional activity on cytotoxic immune cell infiltration into B16-F10 melanoma. We showed that tumors expressing a deleted form of HIF-1α displayed increased levels of NK and CD8+ effector T cells in the tumor microenvironment, which was associated with high levels of CCL2 and CCL5 chemokines. We showed that combining acriflavine, reported as a pharmacological agent preventing HIF-1α/HIF-1β dimerization, dramatically improved the benefit of cancer immunotherapy based on TRP-2 peptide vaccination and anti-PD-1 blocking antibody. In melanoma patients, we revealed that tumors exhibiting high CCL5 are less hypoxic, and displayed high NK, CD3+, CD4+ and CD8+ T cell markers than those having low CCL5. In addition, melanoma patients with high CCL5 in their tumors survive better than those having low CCL5. This study provides the pre-clinical proof of concept for a novel triple combination strategy including blocking HIF-1α transcription activity along vaccination and PD-1 blocking immunotherapy.

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 Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD)

2005 ◽  
Vol 360 (1461) ◽  
pp. 1747-1767 ◽  
Author(s):  
Bruce R Blazar ◽  
William J Murphy
Keyword(s):  
Graft Versus Host Disease ◽  
Opportunistic Infections ◽  
Haematopoietic Stem Cell ◽  
Generation Process ◽  
Host Disease ◽  
Immune Effector ◽  
Effector Cells ◽  
Graft Versus Host ◽  
Donor T Cells ◽  
Donor Graft

Haematopoietic stem cell transplantation (HSCT) offers promise for the treatment of haematological and immune disorders, solid tumours, and as a tolerance inducing regimen for organ transplantation. Allogeneic HSCTs engraftment requires immunosuppression and the anti-tumour effects are dependent upon the immune effector cells that are contained within or generated from the donor graft. However, significant toxicities currently limit its efficacy. These problems include: (i) graft-versus-host disease (GVHD) in which donor T cells attack the recipient resulting in multi-organ attack and morbidity, (ii) a profound period of immune deficiency following HSCT, and (iii) donor graft rejection. Currently available methods to prevent or treat GVHD with systemic immunosuppression can lead to impaired immune recovery, increased opportunistic infections, and higher relapse rates. This review will provide an overview of GVHD pathophysiology and discuss the roles of various cells, pathways, and factors in the GVHD generation process and in the preservation of graft-versus-tumour effects. Variables that need to be taken into consideration in attempting to extrapolate preclinical results to the clinical paradigm will be highlighted.

Sign in / Sign up

Export Citation Format

Share Document