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

doi:10.1016/j.isci.2024.110009

Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia

iScience. 2024 May 17;27(6):110009. doi: 10.1016/j.isci.2024.110009. eCollection 2024 Jun 21.

Authors

Jessie J-Y Chang¹, Samantha L Grimley¹, Bang M Tran², Georgia Deliyannis¹, Carolin Tumpach², An N T Nguyen¹, Eike Steinig^{2

3}, JianShu Zhang¹, Jan Schröder⁴, Leon Caly³, Julie McAuley¹, Sharon L Wong^{5

6}, Shafagh A Waters^{5

6

7}, Timothy P Stinear¹, Miranda E Pitt^{1

8}, Damian Purcell¹, Elizabeth Vincan^{2

3

9}, Lachlan J M Coin^{1

10}

Affiliations

¹ Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
² Department of Infectious Diseases, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
³ Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
⁴ Computational Sciences Initiative (CSI), The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
⁵ Molecular and Integrative Cystic Fibrosis Research Centre, University of New South Wales, Sydney, NSW 2052, Australia.
⁶ School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.
⁷ Department of Respiratory Medicine, Sydney Children's Hospital, Sydney, NSW 2031, Australia.
⁸ Australian Institute for Microbiology and Infection, University of Technology Sydney, Sydney, NSW 2007, Australia.
⁹ Curtin Medical School, Curtin University, Perth, WA 6102, Australia.
¹⁰ Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia.

Abstract

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.

Keywords: Immune response; Immunology; Transcriptomics; Virology.