SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids

Chau, C. W.; To, A.; Au-Yeung, R. K. H.; Tang, K.; Xiang, Y.; Ruan, D.; Zhang, L.; Wong, H.; Zhang, S.; Au, M. T.; Chung, S.; Song, E.; Choi, D.-H.; Liu, P.; Yuan, S.; Wen, C.; Sugimura, R.

doi:10.1101/2024.03.20.585837

bioRxiv · 10.1101/2024.03.20.585837

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids

Chau, C. W.·To, A.·Au-Yeung, R. K. H.·Tang, K.·Xiang, Y.·Ruan, D.·Zhang, L.·Wong, H.·Zhang, S.·Au, M. T.·Chung, S.·Song, E.·Choi, D.-H.·Liu, P.·Yuan, S.·Wen, C.·Sugimura, R.

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Abstract

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

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Chau, C. W., To, A., Au-Yeung, R. K. H., Tang, K., Xiang, Y., Ruan, D., Zhang, L., Wong, H., Zhang, S., Au, M. T., Chung, S., Song, E., Choi, D.-H., Liu, P., Yuan, S., Wen, C., Sugimura, R.. 2024-03-21. SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids. https://doi.org/10.1101/2024.03.20.585837

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