Innate immune surveillance in coronavirus disease-2019 (COVID-19)

Abstract

Severe SARS-CoV-2 infection is characterised by an unbalanced immune response, excessive inflammation, and respiratory distress syndrome, often leading to multiorgan failure death. This study examines the roles number of innate immune membrane-bound and soluble proteins in SARS-CoV-2 infection, including lung surfactant protein D (SP-D), dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN), complement component 1 q (C1q), C4b-binding protein (C4BP), factor H (FH), and properdin (Factor P/FP). We hypothesised that SP-D, C1q, C4BP, FH, and FP can play protective roles in the immune surveillance against SARS-CoV-2 infection, where hyperinflammation contributes to the disease severity. SP-D and DC-SIGN are C-type lectin receptors involved in pathogen recognition. SP-D clears pulmonary pathogens, while DC-SIGN involves plays role in many viral infections. Both interact with SARS-CoV-2. The study investigates the possible role of recombinant fragment human SP-D (rfhSP-D) in the interaction between DS-SIGN and SARS-CoV-2. We found that rfhSP-D binds to the SARS-CoV-2 Spike protein, enhancing viral binding and uptake in DC-SIGN -expressing cells. Additionally, rfhSP-D reduces pro-inflammatory cytokines in macrophage-like cells. The roles of C1q and C4BP in SARS-CoV-2 infection were also explored. Both proteins directly bind to the SARS-CoV-2 Spike protein, reducing viral attachment and entry into A549 cells expressing human ACE2 and TMPRSS2. Treatment with C1q and C4BP led to the downregulation of pro-inflammatory cytokines, suggesting their potential in mitigating the inflammatory response. Furthermore, the study assessed the impact of FH and FP on SARS-CoV-2 infection. FH inhibited viral binding and cell entry, attenuating the infection-associated inflammatory response. Conversely, FP promoted viral cell entry, binding, and immune response, potentially influencing infection severity. In conclusion, the study highlights the intricate interplay of innate immune proteins in SARS-CoV- 2 infection. The findings suggest differential modulatory effects of rfhSP-D, C1q, C4BP, FH, and FP in SARS-CoV-2 infections and offer promising therapeutic interventions targeting these factors. Further in vivo research is required to understand the underlying mechanisms and explore their potential clinical applications.