A5037267534- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Phagocytosis and Immune Regulation
- RNA Interference and Gene Delivery
- Fungal Infections and Studies
- Hematopoietic Stem Cell Transplantation
- Antifungal resistance and susceptibility
- Galectins and Cancer Biology
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Reproductive tract infections research
- Viral Infectious Diseases and Gene Expression in Insects
- Chemokine receptors and signaling
- Phytoplasmas and Hemiptera pathogens
- Toxoplasma gondii Research Studies
- Vector-borne infectious diseases
- Cytokine Signaling Pathways and Interactions
- Plant Pathogens and Fungal Diseases
- Peptidase Inhibition and Analysis
- Clostridium difficile and Clostridium perfringens research
- Platelet Disorders and Treatments
Washington University in St. Louis
2011-2025
Successful infection by fungal pathogens depends on subversion of host immune mechanisms that detect conserved cell wall components such as beta-glucans. A less common polysaccharide, alpha-(1,3)-glucan, is a constituent most respiratory and has been correlated with pathogenicity or linked directly to virulence. However, the precise mechanism which alpha-(1,3)-glucan promotes virulence unknown. Here, we show present in outermost layer Histoplasma capsulatum yeast contributes pathogenesis...
The phagolysosome is perhaps the most effective antimicrobial site within macrophages due both to its acidity and variety of hydrolytic enzymes. Few species pathogens survive multiply in these vesicles. However, one strategy for microbial survival would be induce a higher pH organelles, thus interfering with activity many lysosomal Altering intravesicular milieu might also profoundly influence antigen processing, drug delivery, activity. Here we report first example an organism proliferating...
CD47, an ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often upregulated by hematologic and solid cancers to evade surveillance. Development CD47-targeted modalities hindered the ubiquitous expression target, leading rapid drug elimination hemotoxicity including anemia. To overcome such liabilities, we have developed fully human bispecific antibody, NI-1701, designed coengage CD47 CD19 selectively on B cells....
The cell surface of Chlamydia psittaci seems important for establishing infection since (i) UV-treated elementary bodies (EB) attach to and are ingested by L cells (ii) heat or antibody treatment decreases attachment promotes the fusion chlamydiae-containing phagosomes with lysosomes in macrophages. In studies reported here, [3H]uridine-labeled EB also persisted mouse resident peritoneal macrophages cells, suggesting that phagosome-lysosome is inhibited. We therefore chose investigate...
The yeast form of the dimorphic fungus Histoplasma capsulatum survives within macrophages after phagocytosis. To do so, it must avoid, inhibit, or resist a variety toxic oxygen metabolites. Using ferricytochrome c reduction to assay superoxide release, we examined response mouse various H. strains. Doses zymosan as low 20 particles per macrophage elicited superoxide, whereas failed induce even at 160 cells macrophage. This phenomenon was observed with two virulent strains (G217B and G186A)...
Intracellular survival of Chlamydia psittaci is in part dependent on the ability organism to thwart phagolysosome formation. Circumvention fusion could be either localized chlamydia-laden vacuoles or generalized all phagosomes host cell. To determine which these modes operation chlamydia elementary and reticulate bodies protect Saccharomyces cerevisiae from degradation macrophage phagolysosomes was examined via acridine orange Giemsa staining. No statistically significant difference evident...
Abstract The issue of whether or not phagocytized Histoplasma capsulatum yeasts evade phagosome-lysosome fusion (P-LF) has been debated by several investigators. To resolve this problem, yet avoid drawbacks associated with the conventional assays P-LF (electron microscopy and acridine orange assay), we used fluorescein isothiocyanate-labeled dextran (FITC-dextran) to monitor in macrophage-like cell line P388D1.D2. Controls indicated that FITC-dextran could be distinguish between evasion...
Mobilized peripheral blood has become the primary source of hematopoietic stem and progenitor cells (HSPCs) for cell transplantation, with a 5-day course granulocyte colony-stimulating factor (G-CSF) as most common regimen used HSPC mobilization. The CXCR4 inhibitor plerixafor is more rapid mobilizer, yet not potent enough when single agent, thus emphasizing need faster acting agents predictable mobilization responses fewer side effects. We sought to improve transplantation by developing new...
Point-of-care manufacture of chimeric antigen receptor (CAR)-T cells can significantly reduce the time from apheresis to infusion. We conducted a dual-institution phase I trial aimed evaluating safety and feasibility this manufacturing model. CASE 2417 was clinical trial. Adults with relapsed or refractory CD19 positive non-Hodgkin lymphoma (R/R NHL) treated ≥2 prior systemic therapies were eligible. MB-CART-19 is an anti-CD19 CAR T-cell product manufactured using CliniMACS Prodigy device...
We evaluated P388D1 macrophagelike cells as model host for studying the intracellular survival and strain-specific virulence of Histoplasma capsulatum. Previously characterized strains which were virulent mice destroyed monolayers these within a few days. In contrast, related avirulent "smooth" variants failed to do so even after 20 days, although they persisted at least 7 On basis this observation, we developed quantitative radiolabel assay use an initial screen virulence. Another cell type...
Described herein is a first-in-man attempt to both genetically modify T cells with an imagable suicide gene and track these transduced donor in allogeneic stem cell transplantation recipients using noninvasive positron emission tomography/computerized tomography (PET/CT) imaging. A encoding human CD34-Herpes Simplex Virus-1-thymidine kinase (CD34-TK75) fusion enabled enrichment of retrovirally (TdT), control graft-versus-host disease imaging TdT migration expansion vivo mice man. Analysis...
Many Histoplasma capsulatum strains spontaneously give rise to variants during broth culture or subsequent ingestion by epithelial cells. Unlike their parents, these are defective in killing macrophages and lack a major cell wall constituent, alpha-(1,3)-glucan. Inside macrophages, where the can persist for several weeks, they adopted an unusual morphology strikingly similar that reported tissues of persistently infected humans animals. These yeasts were often enlarged misshapen...
Clinical trials increasingly incorporate suicide genes either as direct lytic agents for tumors or safety switches in therapies based on genetically modified cells. Suicide can also be used non-invasive reporters to monitor the biological consequences of administering cells patients and gather information relevant patient safety. These therapeutic outcomes addressable by early clinical intervention. As an example, our recent trial (18)F-9-(4-fluoro-3-hydroxymethylbutyl)guanine ((18)FHBG)...
Many Histoplasma capsulatum strains have α-(1,3)-glucan in their cell walls and spontaneously produce variants that lack this polymer. The variants, contrast to the parents, exist aberrant shapes within macrophages. Here, ultrastructure of parental variant was examined. All yeasts had identical electron-lucent, thick when grown broth culture. However, ingestion by either macrophages or hamster trachea epithelial (HTE) cells caused become electron-dense, thin, sinuous. Parental remained...