Cytokine-Induced Modulation of SARS-CoV2 Receptor Expression in Primary Human Nasal Epithelial Cells.

Mahnaz Ramezanpour,Karen Hon,Peter-John Wormald,Sarah Vreugde,George Spyro Bouras,Harrison Bolt,Alkis James Psaltis

doi:10.3390/pathogens10070848

Abstract

Background: Viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) via the spike protein enables endocytosis into host cells using the ACE2 receptor and TMPRSS2. The frequent upper respiratory tract symptoms of COVID-19 and the localization of the virus to the nasopharynx, the most common site of swabbing, indicate that the sinonasal mucosa may play an important role in SARS-CoV2 infection and viral replication. Methods: This paper investigates the presence of ACE2 receptor and TMPRESS2 expression in the primary human nasal epithelial cells (HNECs) from the following: chronic rhinosinusitis without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP) and control (non-CRS) patients, and maps the expression changes when exposed to Th1, Th2, Th17-associated cytokines. Results: We found that ACE2 and TMPRSS2 expression was higher in control HNECs than CRSwNP HNECs, and that both ACE2 and TMPRSS2 were downregulated further by Th2 cytokines in CRSwNP HNECs. Conclusions: This indicates an immune dysregulated state of CRSwNP mucosa, which normally contributes to a chronic inflammatory state, and might support an altered susceptibility to SARS-CoV2 infection and transmission.

Highlights

The global pandemic following the outbreak of coronavirus disease of 2019 (COVID19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a serious health threat
This study shows that angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 expression in human sinonasal epithelial cells differs depending on the host’s sinus mucosa pathological state
This dysregulated state supports the findings that ACE2 expression is lower in Chronic rhinosinusitis (CRS) patients

Summary

Introduction

The global pandemic following the outbreak of coronavirus disease of 2019 (COVID19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a serious health threat. Once the SARS spike protein binds to the ACE2 receptor, it becomes more susceptible to host cell proteolytic digestion [5] This cleavage is required for efficient complex formation of the S protein with the ACE2 receptor, facilitating virus uptake [6]. ACE2 and TMPRSS2 expression has been demonstrated in many different cells and tissues throughout the body, not just lung and vascular epithelium [8] This suggests a potential role for ACE2 in viral uptake and replication by multiple cell types and the involvement of multiple organ systems [7], increasing the potential for immune dysregulation. Viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) via the spike protein enables endocytosis into host cells using the ACE2 receptor and TMPRSS2. Conclusions: This indicates an immune dysregulated state of CRSwNP mucosa, which normally contributes to a chronic inflammatory state, and might support an altered susceptibility to SARS-CoV2 infection and transmission.

Methods

Results

Conclusion