The emergence of goblet inflammatory or ITGB6hinasal progenitor cells determines age-associated SARS-CoV-2 pathogenesis

Autor: Maximillian Woodall, Ana-Maria Cujba, Kaylee B. Worlock, Katie-Marie Case, Tereza Masonou, Masahiro Yoshida, Krzysztof Polanski, Ni Huang, Rik G. H. Lindeboom, Lira Mamanova, Liam Bolt, Laura Richardson, Samuel Ellis, Machaela Palor, Thomas Burgoyne, Andreia Pinto, Dale Moulding, Timothy D. McHugh, Aarash Saleh, Eliz Kilich, Puja Mehta, Chris O’Callaghan, Jie Zhou, Wendy Barclay, Paolo De Coppi, Colin R. Butler, Heloise Vinette, Sunando Roy, Judith Breuer, Rachel C. Chambers, Wendy E. Heywood, Kevin Mills, Robert E. Hynds, Sarah A. Teichmann, Kerstin B. Meyer, Marko Z. Nikolić, Claire M. Smith
Rok vydání: 2023
Popis: Children infected with SARS-CoV-2 rarely progress to respiratory failure, but the risk of mortality in infected people over 85 years of age remains high, despite vaccination and improving treatment options. Here, we take a comprehensive, multidisciplinary approach to investigate differences in the cellular landscape and function of paediatric (70y) nasal epithelial cells experimentally infected with SARS-CoV-2. Our data reveal that nasal epithelial cell subtypes show different tropism to SARS-CoV-2, correlating with age, ACE2 and TMPRSS2 expression. Ciliated cells are a viral replication centre across all age groups, but a distinct goblet inflammatory subtype emerges in infected paediatric cultures, identifiable by high expression of interferon stimulated genes and truncated viral genomes. In contrast, infected elderly cultures show a proportional increase in ITGB6hiprogenitors, which facilitate viral spread and are associated with dysfunctional epithelial repair pathways.Graphical Abstract
Databáze: OpenAIRE