Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia
Jessie J.-Y. Chang,
Samantha L. Grimley,
Bang M. Tran,
Georgia Deliyannis,
Carolin Tumpach,
An N.T. Nguyen,
Eike Steinig,
JianShu Zhang,
Jan Schröder,
Leon Caly,
Julie McAuley,
Sharon L. Wong,
Shafagh A. Waters,
Timothy P. Stinear,
Miranda E. Pitt,
Damian Purcell,
Elizabeth Vincan,
Lachlan J.M. Coin
Affiliations
Jessie J.-Y. Chang
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Samantha L. Grimley
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Bang M. Tran
Department of Infectious Diseases, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Georgia Deliyannis
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Carolin Tumpach
Department of Infectious Diseases, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
An N.T. Nguyen
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Eike Steinig
Department of Infectious Diseases, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
JianShu Zhang
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Jan Schröder
Computational Sciences Initiative (CSI), The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia
Leon Caly
Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Julie McAuley
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Sharon L. Wong
Molecular and Integrative Cystic Fibrosis Research Centre, University of New South Wales, Sydney, NSW 2052, Australia; School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
Shafagh A. Waters
Molecular and Integrative Cystic Fibrosis Research Centre, University of New South Wales, Sydney, NSW 2052, Australia; School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia; Department of Respiratory Medicine, Sydney Children’s Hospital, Sydney, NSW 2031, Australia
Timothy P. Stinear
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Miranda E. Pitt
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Australian Institute for Microbiology and Infection, University of Technology Sydney, Sydney, NSW 2007, Australia
Damian Purcell
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Elizabeth Vincan
Department of Infectious Diseases, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Curtin Medical School, Curtin University, Perth, WA 6102, Australia
Lachlan J.M. Coin
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; Corresponding author
Summary: Continuous assessment of the impact of SARS-CoV-2 on the host at the cell-type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral-strain and Alpha-variant SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from younger adults (26–32 Y) and older children (12–14 Y) using single-cell RNA-sequencing. Ciliated and secretory-ciliated cells formed the majority of highly infected cell-types, with the latter derived from ciliated lineages. Strong innate immune responses were observed across lowly infected and uninfected bystander cells and heightened in Alpha-infection. Alpha highly infected cells showed increased expression of protein-refolding genes compared with ancestral-strain-infected cells in children. Furthermore, oxidative phosphorylation-related genes were down-regulated in bystander cells versus infected and mock-control cells, underscoring the importance of these biological functions for viral replication. Overall, this study highlights the complexity of cell-type-, age- and viral strain-dependent host epithelial responses to SARS-CoV-2.
