Innate and adaptive immune responses against coronavirus

Abstract

Coronaviruses (CoVs) are a member of the Coronaviridae family with positive-sense single- stranded RNA. In recent years, the CoVs have become a global problem to public health. The immune responses (innate and adaptive immunity) are essential for elimination and clearance of CoVs infections, however, uncontrolled immune responses can result in aggravating acute lung injury and significant immunopathology. Gaining profound understanding about the interaction between CoVs and the innate and adaptive immune systems could be a critical step in the field of treatment. In this review, we present an update on the host innate and adaptive immune responses against SARS-CoV, MERS-CoV and newly appeared SARS-CoV-2.

Keywords: Adaptive immune response; COVID-19; Convalescent plasma therapy; Innate immune response; Monoclonal antibody therapy.

Graphical abstract

Fig. 1

Schematic structure of SARS-CoV-2. SARS-CoV-2 is a spherical or pleomorphic enveloped particles that contain a positive-sense single-stranded RNA with the size of approximately 29.9 kb. The nucleocapsid protein holds the genome of the virus, and the three other proteins, including spike, membrane and envelope proteins, create the viral envelope.

Fig. 2

Type 1 IFN production in monocytes/macrophages and dendritic cells. TLR4 and TLR2 localize on the cell surface, and TLR3, TLR7 and TLR8 localize in the endosome. TLRs signaling initiate upon ligand binding. TLR2 and TLR7/8 engagement induce formation of MyD88, IRAK1 and IRAK4. IRAKs then activate TRAF6 and TAK1. TAK1 leads to the activation of MAPKs and IKK complex consisting of NEMO, IKKα and IKKβ. The MAPK and IKK complex activation lead to AP-1 and NF-kB transcription factor activation, respectively. TLR7 and TLR8 can also induce IRF3 transcription factor activation. TLR3 requires TRIF for IRF3 phosphorylation, which this adaptor protein interacts with IKKi, TBK1. TRAM is required for signal transduction from TLR4 to TRIF, and TRAP is required for signal transduction from TLR4 to MyD88. Finally, transcription factors move into the nucleus and stimulate gene expression. IRF3 and IRF7 induce type 1 IFNs genes expression, and AP-1 and NF-kB induce pro-inflammatory cytokines genes expression.

Fig. 3

The innate and adaptive immune responses against coronavirus (CoV) infection. The induction of neutrophils, monocytes/macrophages and dendritic cells results in production of various pro-inflammatory cytokines which so-called “cytokine storm”. This process leads to lung immunopathology. Specific CD + Tcells, Th1 and Th17, may be activated and exacerbate lung injury. Cytotoxic T-lymphocyte (CTL) contributes to virus clearance by lysis of infected cells. B cells produce virus specific antibodies and neutralize viruses.