Single-cell analysis of human airway epithelium identifies cell type-specific responses to Aspergillus and Coccidioides .

Autor: Harding AT; Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge MA.; Department of Microbiology, Harvard Medical School, Cambridge MA., Crossen AJ; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Reedy JL; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Basham KJ; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Hepworth OW; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Zhang Y; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA USA., Shah VS; Harvard Stem Cell Institute, Cambridge, MA, USA.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Klarman Cell Observatory, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA., Harding HB; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Surve MV; Harvard Stem Cell Institute, Cambridge, MA, USA.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Simaku P; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Kwaku GN; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Jensen KN; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Otto Y; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA., Ward RA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Thompson GR; Division of Infectious Diseases, and Departments of Internal Medicine and Medical Microbiology and Immunology, University of California-Davis, Sacramento, CA, USA., Klein BS; Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.; Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.; Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA., Rajagopal J; Harvard Stem Cell Institute, Cambridge, MA, USA.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Klarman Cell Observatory, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA., Sen P; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Transplant, Oncology, and Immunocompromised Host Group, Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Dana-Farber Cancer Institute, Boston, MA, USA., Haber AL; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA USA., Vyas JM; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 13. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1101/2024.09.09.612147
Abstrakt: Respiratory fungal infections pose a significant threat to human health. Animal models do not fully recapitulate human disease, necessitating advanced models to study human-fungal pathogen interactions. In this study, we utilized primary human airway epithelial cells (hAECs) to recapitulate the lung environment in vitro and investigate cellular responses to two diverse, clinically significant fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii . To understand the mechanisms of early pathogenesis for both fungi, we performed single-cell RNA sequencing of infected hAECs. Analysis revealed that both fungi induced cellular stress and cytokine production. However, the cell subtypes affected and specific pathways differed between fungi, with A. fumigatus and C. posadasii triggering protein-folding-related stress in ciliated cells and hypoxia responses in secretory cells, respectively. This study represents one of the first reports of single-cell transcriptional analysis of hAECs infected with either A. fumigatus or C. posadasii , providing a vital dataset to dissect the mechanism of disease and potentially identify targetable pathways.
Databáze: MEDLINE