In Vitro and In Vivo Crosstalk between Type I IFN and IL-8 Responses in SARS-CoV-2 Infection

Abstract

COVID-19 patients show characteristic over-expression of different cytokines that may interfere with the interferon (IFN) response, delaying its production. Within the overexpressed cytokines, IL-8 plays a key role, and it may impede IFN-I activation. PBMC from eight healthy donors were exposed to 2019-nCoV/Italy-INMI1 isolate and supernatants/cells were collected at different time points; the production of either IFN-alpha or IL-8 was assessed. The same analysis was performed on plasma samples obtained from 87 COVID-19 patients. Antagonism between IFN-alpha and IL-8 was observed, since in those PBMC with medium or high IL-8 levels, IFN-α levels were low. The same scenario was observed in SARS-CoV-2-infected patients that were divided into three groups based on IL-8 low, medium and high levels; the correlation between low levels of IFN-α and high levels of IL-8 was statistically significant in both the IL-8 medium and IL-8 high group. Overall, our results showed a crosstalk/antagonism between IL-8 and IFN-alpha in PBMC from healthy donors challenged with SARS-CoV-2 and inversely proportional IFN-alpha levels to IL-8 concentrations detected in plasma samples from COVID-19 patients, suggesting that the impairment of the innate immune response in COVID-19 patients may be linked to a dysregulated cytokine response, namely through IL-8 production.

Keywords

• IFN-I
• IL-8
• SARS-CoV-2
• crosstalking
• antagonism
• COVID-19