tetano
Editor, Senior Moderator
Front Immunol
. 2021 Oct 4;12:741502.
doi: 10.3389/fimmu.2021.741502. eCollection 2021.
Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions
Mai M Abdelmoaty[SUP] 1 2 [/SUP], Pravin Yeapuri[SUP] 1 [/SUP], Jatin Machhi[SUP] 3 [/SUP], Katherine E Olson[SUP] 3 [/SUP], Farah Shahjin[SUP] 3 [/SUP], Vikas Kumar[SUP] 4 [/SUP], You Zhou[SUP] 5 [/SUP], Jingjing Liang[SUP] 6 [/SUP], Kabita Pandey[SUP] 3 [/SUP], Arpan Acharya[SUP] 3 [/SUP], Siddappa N Byrareddy[SUP] 3 [/SUP], R Lee Mosley[SUP] 3 [/SUP], Howard E Gendelman[SUP] 3 [/SUP]
Affiliations
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.
. 2021 Oct 4;12:741502.
doi: 10.3389/fimmu.2021.741502. eCollection 2021.
Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions
Mai M Abdelmoaty[SUP] 1 2 [/SUP], Pravin Yeapuri[SUP] 1 [/SUP], Jatin Machhi[SUP] 3 [/SUP], Katherine E Olson[SUP] 3 [/SUP], Farah Shahjin[SUP] 3 [/SUP], Vikas Kumar[SUP] 4 [/SUP], You Zhou[SUP] 5 [/SUP], Jingjing Liang[SUP] 6 [/SUP], Kabita Pandey[SUP] 3 [/SUP], Arpan Acharya[SUP] 3 [/SUP], Siddappa N Byrareddy[SUP] 3 [/SUP], R Lee Mosley[SUP] 3 [/SUP], Howard E Gendelman[SUP] 3 [/SUP]
Affiliations
- PMID: 34671355
- PMCID: PMC8521106
- DOI: 10.3389/fimmu.2021.741502
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.