Search results for "Marr"

The Anti-apoptotic Murine Cytomegalovirus Protein vMIA-m38.5 Induces Mast Cell Degranulation.

2020

Mast cells (MC) represent "inbetweeners" of the immune system in that they are part of innate immunity by acting as first-line sentinels for environmental antigens but also provide a link to adaptive immunity by secretion of chemokines that recruit CD8 T cells to organ sites of infection. An interrelationship between MC and cytomegalovirus (CMV) has been a blank area in science until recently when the murine model revealed a role for MC in the resolution of pulmonary infection by murine CMV (mCMV). As to the mechanism, MC were identified as a target cell type of mCMV. Infected MC degranulate and synthesize the CC-chemokine ligand-5 (CCL-5), which is released to attract protective virus-spec…

The clinical impact of PCR‐based point‐of‐care diagnostic in respiratory tract infections in children

2020

Abstract Background Children are commonly affected by respiratory tract infections. Based on clinical symptoms, laboratory evaluation, and imaging, the causative pathogen often cannot be delineated. Point‐of‐care‐testing systems that provide an opportunity for fast detection of common viruses and some bacteria can therefore influence treatment's options. We aimed to examine whether the Biofire® FilmArray® has an effect on antibiotic treatment, duration of antibiotic therapy, and length of hospital stay within a pediatric cohort. Methods We included children who were admitted to inpatient treatment with an acute respiratory tract infection from 02/2017 to 04/2018 using the FA respiratory pan…

Enhancement of Antigen Presentation by Deletion of Viral Immune Evasion Genes Prevents Lethal Cytomegalovirus Disease in Minor Histocompatibility Ant…

2020

Hematoablative treatment followed by hematopoietic cell transplantation (HCT) for reconstituting the co-ablated immune system is a therapeutic option to cure aggressive forms of hematopoietic malignancies. In cases of family donors or unrelated donors, immunogenetic mismatches in major histocompatibility complex (MHC) and/or minor histocompatibility (minor-H) loci are unavoidable and bear a risk of graft-vs.-host reaction and disease (GvHR/D). Transient immunodeficiency inherent to the HCT protocol favors a productive reactivation of latent cytomegalovirus (CMV) that can result in multiple-organ CMV disease. In addition, there exists evidence from a mouse model of MHC class-I-mismatched GvH…

Insufficient Antigen Presentation Due to Viral Immune Evasion Explains Lethal Cytomegalovirus Organ Disease After Allogeneic Hematopoietic Cell Trans…

2020

Reactivation of latent cytomegalovirus (CMV) poses a clinical problem in transiently immunocompromised recipients of hematopoietic cell (HC) transplantation (HCT) by viral histopathology that results in multiple organ manifestations. Compared to autologous HCT and to syngeneic HCT performed with identical twins as HC donor and recipient, lethal outcome of CMV infection is more frequent in allogeneic HCT with MHC/HLA or minor histocompatibility loci mismatch between donor and recipient. It is an open question if a graft-versus-host (GvH) reaction exacerbates CMV disease, or if CMV exacerbates GvH disease (GvHD), or if interference is mutual. Here we have used a mouse model of experimental HC…

2016

Psoriasis is an autoimmune skin disease that is associated with aberrant activity of immune cells and keratinocytes. In mice, topical application of TLR7/8 agonist IMQ leads to a skin disorder resembling human psoriasis. Recently, it was shown that the IL-23/ IL-17 axis plays a deciding role in the pathogenesis of human psoriasis, as well as in the mouse model of IMQ-induced psoriasis-like skin disease. A consequence of IL-17A production in the skin includes increased expression and production of IL-6, resulting in the recruitment of neutrophils and other myelomonocytic cells to the site of inflammation. To further investigate and characterize the exact role of IL-6 signaling in myelomonocy…

2018

Protein tyrosine phosphatases and glucocorticoids are known to regulate allergic and antiallergic action in activated mast cells. Here we provide RNA sequencing and quantitative real-time PCR data from bone marrow derived mast cells, for wild-type and PEST-domain-enriched tyrosine phosphatase (PEP) null mice, activated by immunoglobulin E sensitization and dinitrophenol treatment, and additionally treated with the glucocorticoid dexamethasone. The transcriptomics experiment was performed in duplicate with a total of 16 samples (GSE108972).

Myeloid leukemia with transdifferentiation plasticity developing from T-cell progenitors

2016

Unfavorable patient survival coincides with lineage plasticity observed in human acute leukemias. These cases are assumed to arise from hematopoietic stem cells, which have stable multipotent differentiation potential. However, here we report that plasticity in leukemia can result from instable lineage identity states inherited from differentiating progenitor cells. Using mice with enhanced c-Myc expression, we show, at the single-cell level, that T-lymphoid progenitors retain broad malignant lineage potential with a high capacity to differentiate into myeloid leukemia. These T-cell-derived myeloid blasts retain expression of a defined set of T-cell transcription factors, creating a lymphoi…

Depleted uranium induces human carcinogenesis involving the immune and chaperoning systems: Realities and working hypotheses

2019

Abstract Cancer is caused by a combination of factors, genetic, epigenetics and environmental. Among the latter, environmental pollutants absorbed by contact, inhalation, or ingestion are major proven or suspected culprits. Depleted uranium (DU) is one of them directly pertinent to the military and civilians working in militarized areas. It is considered a weak carcinogen but its implication in cancer development in exposed individuals is supported by various data. Since not all subjects exposed to DU develop cancer, it is likely that DU-dependent carcinogenesis requires cofactors, such as genetic predisposition and deficiencies of the chaperoning and immune systems. It is of the essence to…

A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival

2016

AbstractMultiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then sel…

Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients

2017

The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs. 38%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)…