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HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections.
Cell Rep
December 2024
Max Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, Austria. Electronic address:
Histone deacetylases (HDACs) contribute to shaping many aspects of T cell lineage functions in anti-infective surveillance; however, their role in fungus-specific immune responses remains poorly understood. Using a T cell-specific deletion of HDAC1, we uncover its critical role in limiting polarization toward Th17 by restricting expression of the cytokine receptors gp130 and transforming growth factor β receptor 2 (TGF-βRII) in a fungus-specific manner, thus limiting Stat3 and Smad2/3 signaling. Controlled release of interleukin-17A (IL-17A) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is vital to minimize apoptotic processes in renal tubular epithelial cells in vitro and in vivo.
View Article and Find Full Text PDFFatal dermatophytic pseudomycetoma in a patient with non-HIV CD4 lymphocytopenia.
Emerg Microbes Infect
December 2023
Department of Dermatology and Venerology, Peking University First Hospital, Beijing, People's Republic of China.
Dermatophytic pseudomycetoma is a rare invasive infection, involving both immunocompetent and immunocompromised individuals. Since the discovery of inherited immune disorders such as the impairment of gene, extended dermatophyte infections are mostly ascribed to any of these host factors. This study is to present and explore the potential causes in a fatal dermatophytic pseudomycetoma patient.
View Article and Find Full Text PDFInvasive fungal infections are a major cause of disease and death in immunocompromised hosts, including patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Recovery of adaptive immunity after HSCT correlates strongly with recovery from fungal infection. Using initial selection of lymphocytes expressing the activation marker CD137 after fungal stimulation, we rapidly expanded a population of mainly CD4+ T cells with potent antifungal characteristics, including production of tumor necrosis factor α, interferon γ, interleukin-17, and granulocyte-macrophage colony stimulating factor.
View Article and Find Full Text PDFThe domestic pig as human-relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus.
Eur J Immunol
November 2020
Institute of Immunology, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Pulmonary mucosal immune response is critical for preventing opportunistic Aspergillus fumigatus infections. Although fungus-specific CD4 T cells in blood are described to reflect the actual host-pathogen interaction status, little is known about Aspergillus-specific pulmonary T-cell responses. Here, we exploit the domestic pig as human-relevant large animal model and introduce antigen-specific T-cell enrichment in pigs to address Aspergillus-specific T cells in the lung compared to peripheral blood.
View Article and Find Full Text PDFFungus-Specific CD4 T Cells as Specific Sensors for Identification of Pulmonary Fungal Infections.
Mycopathologia
February 2018
Department of Cellular Immunology, Clinic for Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Patients with cystic fibrosis (CF) suffer from chronic lung infections, caused by bacterial, viral or fungal pathogens, which determine morbidity and mortality. The contribution of individual pathogens to chronic disease and acute lung exacerbations is often difficult to determine due to the complex composition of the lung microbiome in CF. In particular, the relevance of fungal pathogens in CF airways remains poorly understood due to limitations of current diagnostics to identify the presence of fungal pathogens and to resolve the individual host-pathogen interaction status.
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