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).