SARS-CoV-2 spike fails to induce inflammation in paediatric airway cells
Respirology
; 28(Supplement 2):107, 2023.
Article
in English
| EMBASE | ID: covidwho-2315372
ABSTRACT
Introduction/Aim:
The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enables it to recognise and bind host receptors. These dynamics have been modelled in various cell types and immortalised lines, but rarely in primary airway epithelial cells (AEC), and especially not in children. Therefore, this study on AEC recapitulated earlier work testing the hypothesis that exposure to the spike protein would induce airway immune responses in airway cells of young children. Method(s) Primary AEC monolayer cultures from healthy children (n = 5, <10 years old, males = 5) were exposed to the spike protein S1 subunit (0.01, 1, and 10 mug/mL) over 48 h. Induced inflammatory cytokines, interleukin (IL) 6 and IL8, and viral-associated chemokines, CCL5 and CXCL10 were measured via ELISA. Basal receptor gene expression (ACE2 and TMPRSS2) was measured in monolayer (n = 5) and terminally differentiated (air-liquid interface [ALI];n = 5) cell models as well as in ex-vivo cells obtained directly from nasal brushings (n = 71). Generalised linear modelling, accounting for individual variability, identified any statistical difference (p < 0.05). Result(s) Exposure to the spike protein resulted in no increase in IL6 and IL8 production, however a significant (p < 0.05) decrease was observed at the highest dose tested (10 mug/mL). CXCL10 was only significantly induced at the highest dose (10 mug/mL) whereas CCL5 was not induced. When compared to ex-vivo samples, baseline expression of ACE2 and TMPRSS2 was significantly lower in monolayer cultures (~57- and ~4- fold respectively, p < 0.05), whereas ALI cultures had similar expression levels. Conclusion(s) The use of recombinant spike protein and monolayer cultures appears to not accurately model SARS-CoV-2 spike protein-host interactions. The lack of inflammatory responses may be attributed to the lower receptor gene expression in monolayer cultures. Future studies should utilise live virus and ALI cultures as a more biologically relevant model to study virus-host interactions.
airway epithelium cell; child; conference abstract; controlled study; drug megadose; enzyme linked immunosorbent assay; ex vivo study; gene expression; human; human cell; immune response; inflammation; male; monolayer culture; nonhuman; protein expression; receptor gene; Severe acute respiratory syndrome coronavirus 2; spike; virus cell interaction; chemokine; cytokine; endogenous compound; gamma interferon inducible protein 10; interleukin 6; interleukin 8; rantes; transmembrane protease serine 2; virus spike protein
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Respirology
Year:
2023
Document Type:
Article
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