Silent hypoxia has emerged as a unique feature of coronavirus disease 2019 (COVID-19). In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. We find that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity. These findings potentially explain the silent hypoxia formation in COVID-19 patients, and suggest a possible intervention strategy by targeting the AhR pathway.
【저자키워드】 immunology, Innate immunity, 【초록키워드】 COVID-19, coronavirus disease, coronavirus, hypoxia, SARS-COV-2 infection, interferon, lung, Intervention, Bronchoalveolar lavage fluid, mice, pathway, mucin, mucins, expression, BALF, COVID-19 patients, IFN-γ, macaques, alveolar epithelial cells, Signaling, Aryl hydrocarbon receptor, COVID-19 patient, Activation, severe respiratory syndrome, Transcriptional upregulation, alveolar, membrane-bound, Affect, lung capacity, unique, upregulated, explain, reversed, silent, accumulated, secreted, 【제목키워드】 COVID-19, hypoxia, Signaling, Mucus, Trigger, stimulated,