Virus Caused Imbalance of Type I IFN Responses and Inflammation in COVID-19

Abstract

The global expansion of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the greatest public health challenges and imposes a great threat to human health. Innate immunity plays vital roles in eliminating viruses through initiating type I interferons (IFNs)-dependent antiviral responses and inducing inflammation. Therefore, optimal activation of innate immunity and balanced type I IFN responses and inflammation are beneficial for efficient elimination of invading viruses. However, SARS-CoV-2 manipulates the host's innate immune system by multiple mechanisms, leading to aberrant type I IFN responses and excessive inflammation. In this review, we will emphasize the recent advances in the understanding of the crosstalk between host innate immunity and SARS-CoV-2 to explain the imbalance between inflammation and type I IFN responses caused by viral infection, and explore potential therapeutic targets for COVID-19.

Keywords: COVID-19; SARS-CoV-2; inflammation; innate immunity; type I interferons.

Figure 1

Predicted immune dysregulation in the lung during SARS-CoV-2 infection. After contact with droplets containing SARS-CoV-2, host immune responses are activated in the lung. Activation of immune cell subgroups such as inflammatory macrophages and neutrophils results in the secretion of massive amounts of inflammatory cytokines, including TNF-α, IL-6, IL-8, and CXCLs. In contrast to excessive proinflammatory cytokines, IFNs levels are lower during the early phase of infection.

Figure 2

Regulation of type I IFN responses and inflammation by SARS-CoV-2 and SARS-CoV. An outline of IFN signaling (left) and major inflammatory signaling (right) is shown, annotated with the known mechanisms by which SARS-CoV activates or suppresses signals (gray). Some SARS-CoV-2 proteins have also been confirmed or speculated to interact with these pathways (orange).