Image_4_Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions.jpeg (1.14 MB)

Image_4_Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions.jpeg

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posted on 2021-10-04, 04:49 authored by Mai M. Abdelmoaty, Pravin Yeapuri, Jatin Machhi, Katherine E. Olson, Farah Shahjin, Vikas Kumar, You Zhou, Jingjing Liang, Kabita Pandey, Arpan Acharya, Siddappa N. Byrareddy, R. Lee Mosley, Howard E. Gendelman

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.