Transcriptional dynamics of granulocytes in direct response to incubation with SARS‐CoV‐2

Abstract

Severe coronavirus disease 2019 (COVID‐19) is characterized by acute respiratory distress syndrome and multiple organ dysfunction, in which the host immune response plays a pivotal role. Excessive neutrophil activation and subsequent superfluity of neutrophil extracellular traps (NETs) can lead to tissue damage, and several studies have shown the involvement of neutrophils in severe COVID‐19. However, the detailed responses of each neutrophil subset to SARS‐CoV‐2 infection has not been fully described. To explore this issue, we incubated normal‐density granulocytes (NDGs) and low‐density granulocytes (LDGs) with different viral titers of SARS‐CoV‐2. NDGs form NETs with chromatin fibers in response to SARS‐CoV‐2, whereas LDGs incubated with SARS‐CoV‐2 display a distinct morphology with condensed nuclei and moderate transcriptional changes. Based on these transcriptional changes, we suggest that AGO2 possibly plays a role in LDG regulation in response to SARS‐CoV‐2.

Neutrophil Extracellular Traps and Their Possible Implications in Ocular Herpes Infection

“…Neutrophils are the innate immune cells recruited to sites of viral infections in the most abundance and exhibit both protective and pathologic functions [ 71 , 72 , 73 ]. In antibacterial and antifungal immunity, the role of neutrophils is well characterized.…”

“…Interaction with other immune cell populations, virus internalization and killing, and the release of cytokines, chemokines, and antimicrobial components are all mechanisms by which neutrophils can contribute to pathogen clearance. Although conventionally regarded as a defense mechanism against bacterial infections, recent findings have also implicated NET formation in limiting viral infections [ 7 , 71 , 72 , 73 ]. These virus-induced NETs can both control the virus and damage the host [ 7 , 74 ].…”

“…However, an expanding number of studies indicate that a disproportionate virus-induced NET release can contribute to damage locally as well as systemically. Thus, it is important to explore the mechanisms that control NET formation in the context of viral infection [ 71 , 72 , 73 ].…”

Inhibition of Toll-like receptor 4 and Interleukin-1 receptor prevent SARS-CoV-2 mediated kidney injury

“…Cell injury and the associated signal were evaluated by TUNEL assay [35] and immunostaining of NF-κB p65 subunit and STAT3 using anti-NFκB antibody (Abcam, Cambridge, UK) and anti-STAT3 antibody (Thermo Fisher Scientific), respectively, after fixation with 4% paraformaldehyde. The positive areas of TUNEL staining and immunostaining were measured using the ImageJ software as described [38]. The data were expressed as the mean ± standard error of the mean (SEM) from three independent experiments.…”

“…One hour after exposure, the SARS-CoV-2 solution was removed and replaced with virus-free DMEM. After 0-, 23-and 71-h D. Nakazawa et al cell incubation, the supernatant was then removed and total RNA was extracted from each cell using the RNA isolation regent (see Supplementary Materials) as previously described [38]. First-strand cDNA was synthesized using cDNA Synthesis kit (see Supplementary Materials), and quantitative PCR was performed using qPCR kit (see Supplementary Materials).…”