Med Mycol
Pediatric Hematology and Oncology, Children's Hospital III, Johann Wolfgang Goethe University, Frankfurt, Germany.
Published: July 2009
Invasive aspergillosis remains a serious complication in patients undergoing allogeneic stem cell transplantation. Since it became clear that lymphocytes provide a critical secondary defense against fungi, adoptive transfer of functionally active anti-Aspergillus T cells might be an option to restore adaptive immune effector mechanisms. Using the interferon (IFN)-gamma secretion assay, we isolated human activated T cells upon stimulation with a cellular extract of Aspergillus fumigatus. After a culturing period for 14 days, we could characterize these cells as T(H)1 cells, which also proliferated upon restimulation. The generated cells responded upon stimulation with antigens of A. flavus, A. niger and Penicillium chrysogenum, but not upon activation with Alternaria alternata and Candida albicans. In addition, the cultivated T cells were able to induce damage to A. fumigatus hyphae and showed a reduced alloreactivity compared to unselected CD4+ T cells. We further established a clinical-scale generation of anti-Aspergillus T cells. However, before performing clinical trials, open questions such as which patient population will benefit from adoptive immunotherapy with anti-Aspergillus T cells have to be addressed.
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http://dx.doi.org/10.1080/13693780802169120 | DOI Listing |
Front Cell Infect Microbiol
November 2024
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Objective: The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates the mRNA of the transcription factor, HacA. Previously, we demonstrated that is essential for virulence in a murine model of fungal keratitis (FK), suggesting the pathway could serve as a therapeutic target. Here we investigate the antifungal properties of known inhibitors of the mammalian Ire1 protein both and in a treatment model of FK.
View Article and Find Full Text PDFEBioMedicine
October 2024
Department of Imaging and Pathology, Biomedical MRI Unit/MoSAIC, KU Leuven, 3000, Leuven, Belgium. Electronic address:
Background: Influenza-associated pulmonary aspergillosis (IAPA) is a severe fungal superinfection in critically ill influenza patients that is of incompletely understood pathogenesis. Despite the use of contemporary therapies with antifungal and antivirals, mortality rates remain unacceptably high. We aimed to unravel the IAPA immunopathogenesis as a means to develop adjunctive immunomodulatory therapies.
View Article and Find Full Text PDFMed Mycol J
September 2024
Department of Fungal Infection, National Institute of Infectious Diseases.
The hyphal surface of cells of filamentous fungi is covered with cell wall, which is mainly composed of polysaccharides. Since the cell wall is the first structure to come in contact with the infection host, the environment, and the fungus itself, the elucidation of the cell wall structure and biogenesis is essential for understanding fungal ecology. Among filamentous fungi, the genus Aspergillus is an important group in the industrial, food, and medical fields.
View Article and Find Full Text PDFInt J Infect Dis
May 2024
Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié, Salpêtrière, Service de Parasitologie-Mycologie, Paris, France.
mBio
April 2024
Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Invasive aspergillosis (IA) is a common and deadly mold infection in immunocompromised patients. As morbidity and mortality of IA are primarily driven by poor immune defense, adjunct immunotherapies, such as chimeric antigen receptor (CAR) T cells, are direly needed. Here, we propose a novel approach to generate (AF)-CAR T cells using the single-chain variable fragment domain of monoclonal antibody AF-269-5 and a lentiviral vector system.
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