Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions

Authors

Mai M. Abdelmoaty, University of Nebraska Medical Center, National Research Centre
Pravin Yeapuri, University of Nebraska Medical Center
Jatin Machhi, University of Nebraska Medical Center
Katherine E. Olson, University of Nebraska Medical Center
Farah Shahjin, University of Nebraska Medical Center
Vikas Kumar, University of Nebraska Medical Center
You Zhou, University of Nebraska - LincolnFollow
Jingjing Liang, Case Western Reserve University
Kabita Pandey, University of Nebraska Medical Center
Arpan Acharya, University of Nebraska Medical Center
Siddappa N. Byrareddy, University of Nebraska Medical Center
R. Lee Mosley, University of Nebraska Medical Center
Howard E. Gendelman, University of Nebraska Medical Center

Document Type

Article

Date of this Version

10-4-2021

Citation

Abdelmoaty MM, Yeapuri P, Machhi J, Olson KE, Shahjin F, Kumar V, Zhou Y, Liang J, Pandey K, Acharya A, Byrareddy SN, Mosley RL and Gendelman HE (2021) Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions. Front. Immunol. 12:741502. doi: 10.3389/fimmu.2021.741502

Comments

open access

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.