Innate Immunity to SARS-CoV-2:
The main process by which the innate immune system fights any viral infection is production of type I interferons by the infected cells particularly the plasmacytoid dendritic cells and cytotoxic killing of the viral infected cells by the NK cells(25).
Production of interferons is initiated by recognizing the viral nucleic acid by the pattern recognition receptors (PRRs) such as endosomal Toll like receptors (TLRs) and retinoic acid-inducible gene (RIG) like receptors. After ligand-receptor binding, PRRs stimulate certain adaptor proteins which, in turn leads to the activation of critical down-stream transcription factors, including the interferon regulatory factor (IRF) transcription factor which initiate interferon gene transcription leading to production of interferons. Type I interferons acts by suppressing the viral replication in infected and neighboring cells. Moreover, PRRs activate other signaling pathways such as NF-κB, and AP-1, leading to secretion of many other cytokines and chemokines(32).
The produced chemokines serve in recruiting cells of innate immunity as neutrophils, monocytes, NK cells and dendritic cells which in turn help in producing more chemokines like MIG, IP-10, and MCP-1 which play important role in attracting lymphocytes and initiating the adaptive immune response(33).
The early immune response initiated by SARS-CoV-2 in comparison to other coronaviruses infections was monitored by several studies. For example, a recent in vitro study reported that both SARS and SARS-CoV-2 have equal ability to infect type I and type II pneumocytes and alveolar macrophages with better capability of intracellular replication for SARS-CoV-2 over SARS. However, SARS-CoV-2 was not able to initiate the production of type I, II and III interferons, in addition it had less effective production of other cytokines when compared to SARS immune response at the same early stage of infection. Only 5 cytokines (IL-6, MCP1, CXCL1, CXCL5, and CXCL10/IP10) were expressed by SARS-CoV-2 infection while all the 11 cytokines measured in this study were produced through SARS immune response (34).
Moreover, it was shown that SARS-CoV-2 is associated with less interferons production and increased proinflammatory cytokines release including IL-1B, IL-6, TNF, and IL1RA in a study that investigated the immune response of SARS-CoV-2 in relation to other respiratory viruses such as SARS, MERS, respiratory syncytial virus (RSV), parainfluenza virus 3 (HPIV3), and influenza A virus (IAV). The study involved respiratory cell lines infection, in vivo infection of ferrets as well as lung samples obtained from dead COVID-19 cases(35).
These findings hypothesize that SARS-CoV-2 has an altered immune response compared to the other coronaviruses in term of more capability of intracellular replication in lungs, increased activation of innate immunity associated with higher levels of proinflammatory cytokines as well as high evasion mechanisms abilities that allow it to skip the production of interferons and their antiviral response(16).
On the other side, NK cells play a potential role in fighting viral infection early in the disease before development of adaptive immune response. As an evasion mechanisms of the viruses, the virus infected cells decrease the expression of MHC class I on their surfaces so the immune system could not catch them especially CD8 cytotoxic cells, however, this leads to activation of the NK cells which are inhibited naturally through recognition of MHC class I on the target cells enabling NK cells to exert their cytotoxic actions against the infected cells and hence eradication of the viral infection(25).