| Autor: |
Leibel SL, McVicar RN, Murad R, Kwong EM, Clark AE, Alvarado A, Grimmig BA, Nuryyev R, Young RE, Lee JC, Peng W, Zhu YP, Griffis E, Nowell CJ, Liu K, James B, Alarcon S, Malhotra A, Gearing LJ, Hertzog PJ, Galapate CM, Galenkamp KMO, Commisso C, Smith DM, Sun X, Carlin AF, Croker BA, Snyder EY |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Jan 27. Date of Electronic Publication: 2023 Jan 27. |
| DOI: |
10.1101/2023.01.26.525578 |
| Abstrakt: |
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes an acute respiratory distress syndrome (ARDS) that resembles surfactant deficient RDS. Using a novel multi-cell type, human induced pluripotent stem cell (hiPSC)-derived lung organoid (LO) system, validated against primary lung cells, we found that inflammatory cytokine/chemokine production and interferon (IFN) responses are dynamically regulated autonomously within the lung following SARS-CoV-2 infection, an intrinsic defense mechanism mediated by surfactant proteins (SP). Single cell RNA sequencing revealed broad infectability of most lung cell types through canonical (ACE2) and non-canonical (endocytotic) viral entry routes. SARS-CoV-2 triggers rapid apoptosis, impairing viral dissemination. In the absence of surfactant protein B (SP-B), resistance to infection was impaired and cytokine/chemokine production and IFN responses were modulated. Exogenous surfactant, recombinant SP-B, or genomic correction of the SP-B deletion restored resistance to SARS-CoV-2 and improved viability. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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