ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

Abstract

Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

ACE2 and TAS2R38 receptor expression in pediatric and adult patients in the nasal and oral cavity

“… 2 Initial infection occurs within in the upper airway with increased levels of ACE2 within the neuroepithelium of the nose, 3 explaining the high incidence of anosmia and hyposmia in SARS‐CoV‐2 infections. Studies have implicated ACE2 as major participant in innate immunity 4 and suggested patients on renin‐angiotensin system (RAS) blockers are less likely to have severe disease, 5 , 6 , 7 which re‐enforces how function or prevalence of the receptor may explain disease severity.…”

“…The oral and nasal cavities are in close proximity to these tissues and likely associated with increased inflammation as well. Given ACE2's connection to innate immunity and inflammation,4 it may be upregulated in this patient population.Finally, ACE2 RNA expression may have a minor role in actual protein expression and function in infectivity of SARS-CoV-2. Multiple proteins such as TMPRSS2 are involved in SARS-CoV-2 activity and virulence2 and may play an equal or more important role in describing the differences in age virulence.…”

Biomarker Profiles Associated with COVID-19 Severity and Mortality

“…According to the literature, severe SARS-CoV-2 can trigger an excessive immune response, with massive production of inflammatory cytokines and chemical mediators, known as the cytokine storm [ 4 , 5 , 6 , 7 ]. Cytokine levels rise during the systemic inflammatory response syndrome and may lead to multi-organ failure in some individuals.…”

SARS‐CoV‐2 vaccines: A double‐edged sword throughout rapid evolution of COVID‐19

“…The virus enters host cells by binding to the angiotensin‐converting enzyme 2 (ACE‐2) receptor in most host cells (Singh et al, 2021 ). Once the SARS‐CoV‐2 spike protein binds to ACE‐2, it downregulates its expression, consequently increasing capillary permeability and causing pulmonary damage (Qu et al, 2021 ).…”

“…The virus enters host cells by binding to the angiotensinconverting enzyme 2 (ACE-2) receptor in most host cells (Singh et al, 2021). Once the SARS-CoV-2 spike protein binds to ACE-2, it downregulates its expression, consequently increasing capillary permeability and causing pulmonary damage (Qu et al, 2021). The innate immune system functions as the first line of host defense against pathogens and plays a key role in combating SARS-CoV-2 (Diamond & Kanneganti, 2022).…”