Aspergillus fumigatus infection and fibrosis

烟曲霉感染和纤维化

• 批准号: 10685373
• 负责人: DAVID S ASKEW
• 金额: $ 40.5万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685373
• 关键词: Ablation; Acute; Acute Respiratory Distress Syndrome; Affect; Allergic Bronchopulmonary Aspergillosis; Aspergillosis; Aspergillus; Aspergillus fumigatus; Atmosphere; Behavior; Biological Models; Blood capillaries; COVID-19; Cell Differentiation process; Chronic; Complication; Connective Tissue; Data; Dendritic Cells; Development; Disease; Effectiveness; Environment; Enzymes; Epithelium; Exposure to; Extracellular Matrix; Failure; Fibroblasts; Fibrosis; Foundations; Fright; Gene Expression Profile; Genetic; Genetic Models; Genetic Transcription; Geographic Locations; Germination; Goals; Grant; Growth Factor; Hematogenous; Hematopoietic stem cells; Host Defense; Host Defense Mechanism; Human; Hyphae; Immune; Immune system; Immunocompetent; Immunosuppression; Incidence; Individual; Infection; Inflammatory; Inflammatory Response; Inhalation; Innate Immune System; Knowledge; Life; Light; Lung; Lung infections; Macrophage; Mediator; Molds; Mus; Myelogenous; Myeloid Cells; Opportunistic Infections; Organ Transplantation; Outcome; Outcome Study; Pathogenesis; Pathogenicity; Pathology; Patients; Pneumonia; Population; Process; Production; Pulmonary Fibrosis; Pulmonary vessels; Reaction; Reproduction spores; Severities; Solid; Structural defect; Structure of parenchyma of lung; Testing; Tissues; Transplantation; cell type; cytokine; fungus; immunological status; immunoregulation; immunosuppressed; improved outcome; in vivo; interstitial; long-term sequelae; lung injury; lung pathogen; mouse genetics; mouse model; novel; novel therapeutic intervention; pathogen; pathogenic fungus; pathogenic microbe; repaired; respiratory; response; response to injury; treatment strategy

Aspergillus fumigatus is an environmental mold that is responsible for a life-threatening pneumonia known as invasive aspergillosis. The infection begins with the inhalation of conidia (spores) into the lung. In a healthy individual, the spores are cleared by the immune system. However, in the immunosuppressed population, or patients in the ICU, failure to eradicate the fungus allows the spores to germinate. A. fumigatus releases an armamentarium of degradative enzymes as it grows, resulting in severe damage to the lung parenchyma. Fibroblasts are one of the major cell types that respond to tissue damage. In response to injury, these cells differentiate into an activated state, which is required to stabilize the tissue and promote repair. However, fibroblast activity is not restricted to matrix secretion; emerging evidence suggests that they also possess the ability to detect microbial pathogens and to respond by secreting mediators with the potential to contribute to pathogen clearance. In this grant, we propose to take advantage of unique genetic mouse models that we have developed to determine the contribution of pulmonary fibroblasts to the outcome of A. fumigatus exposure. We hypothesize that fibroblast activation in response to A. fumigatus-induced lung damage amplifies a protective inflammatory response. The proposed aims will test this hypothesis by determining the dynamics of fibroblast activation and deactivation in response to A. fumigatus in both immunocompetent and immunosuppressed mice, the transcriptional response of fibroblasts to A. fumigatus exposure, and the contribution of fibroblasts to pathogenic outcome in a mouse model of fibroblast ablation. The findings of this study will provide new information on mechanisms of host defense against A. fumigatus and potentially other pathogens that damage the human lung. 1

烟曲霉是一种环境霉菌，可导致危及生命的肺炎