Bacille-Calmette-Guerin modulates human macrophage and dendritic cell response to SARS-CoV-2 S-glycoprotein

Background: Given that epidemiological evidence suggests a potential protective role for Bacille-Calmette-Guerin against COVID-19, we aimed to explore whether pre-exposure of human monocyte-derived macrophages and dendritic cells to BCG could modulate their response to SARS-CoV-2 S-glycoprotein. Methods: Dual THP-1 cells containing 2 reporter plasmids for transcription factors NF-κB, and IRF were differentiated into macrophages over 3 days using phorbol 12-myristate 13-acetate, or into dendritic cells over 6 days using commercial monocyte-dencritic cell differentiation media and matured with recombinant tumor necrosis factor-α. Cells were exposed to BCG for 24 h and then stimulated with SARS-CoV-2 S-glycoprotein for 24 hours. Results: Pre-exposure of human macrophages and DCs to BCG increased IRF and NF-kb activation in response to the SARS-CoV-2 S-glycoprotein. Conclusions: Our results showed that pre-exposure of both types of cells to BCG exhibited an increase in inflammatory transcription factors upon stimulation with S-glycoprotein. BCG-induced trained immunity may be an important tool for reducing susceptibility to SARS-CoV-2 infection and severity of COVID-19. Our findings help in the design of future BCG-based therapeutic approaches in the treatment of diseases caused by viral infections.