@article{53a2125c031143039f9c0543d7907714,
title = "Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions",
abstract = "Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.",
keywords = "SARS-CoV-2, cytokine storm, end-organ disease, inflammation, interferon, macrophages, proteomics, transcriptomics",
author = "Abdelmoaty, {Mai M.} and Pravin Yeapuri and Jatin Machhi and Olson, {Katherine E.} and Farah Shahjin and Vikas Kumar and You Zhou and Jingjing Liang and Kabita Pandey and Arpan Acharya and Byrareddy, {Siddappa N.} and Mosley, {R. Lee} and Gendelman, {Howard E.}",
note = "Funding Information: The authors thank the UNMC BSL-3 Core facility for providing all the support required during this study. The authors would also like to thank UNMC Elutriation and Cell Separation Core Facility (Myhanh Che and Na Ly) for providing human monocytes. The authors would also like to thank Dr. Pawel Ciborowski and his research group within the Department of Pharmacology and Experimental Neuroscience at UNMC for discussion and assistance with the proteomic sample preparation. The authors would also like to thank Dr. St Patrick Reid within the Department of Pathology and Microbiology at UNMC for his assistance in the pilot study evaluations. The authors acknowledge the UNMC Mass Spectrometry and Proteomics Core Facility for assistance with the proteomic analysis. The authors would also like to acknowledge the UNMC Flow Cytometry Research Core Facility for assistance with the flow cytometric analysis. The authors would like to thank Dirk Anderson (The Biotech Microscopy Core Research Facility of University of Nebraska-Lincoln) for his assistance with TEM sample preparations. Funding Information: The work was supported, in part, by the University of Nebraska Foundation, which includes donations from the Carol Swarts, M.D. Emerging Neuroscience Research Laboratory, the Margaret R. Larson Professorship, the Frances and Louie Blumkin, and the Harriet Singer Research Donations. We thank Dr. Bradley Britigan, Dean of the College of Medicine at UNMC, for providing funds to support the SARS-CoV-2 studies. The research also received support from National Institutes of Health grants PO1 DA028555, R01 NS36126, PO1 MH64570, P30 MH062261, P20 GM113126, R01 AG043540, and 2R01 NS034239. We also thank the INBRE grant support from 2P20GM103427 for infrastructure research support. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Abdelmoaty, Yeapuri, Machhi, Olson, Shahjin, Kumar, Zhou, Liang, Pandey, Acharya, Byrareddy, Mosley and Gendelman.",
year = "2021",
month = oct,
day = "4",
doi = "10.3389/fimmu.2021.741502",
language = "English (US)",
volume = "12",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}