Modulation of the innate and adaptive immune system during coronavirus infection

Abstract

The SARS-CoV-2 virus pandemic has put a massive struggle on health care systems. The only therapeutical option at the moment is vaccination. Viral mutation may reduce the efficacy of vaccines. We analyzed if a prophylactic immune cell activation using the bacterial extract Broncho Vaxom (BV) is beneficial during a coronavirus infection. To test our hypothesis we used a mouse coronavirus (MCoV) belonging to the same virus subfamily as SARS-CoV-2. BV was applied for 10 days before MCoV challenge. Viral load was significantly reduced in BV treated animals on day 4 and 10 compared to control (qPCR and histochemistry). BV treated animals had significantly reduced TUNEL positive cells at day 4 and 10 and cleaved caspase 3 positive cells at day 10. To analyze involved pathways in this antiapoptotic protection we performed RNA sequencing on healthy and virus infected lungs with or without BV at day 4. We found that BV treatment lead to a phenotype closer to healthy lung tissue then to disease tissue with already reduced interferon expression. Mechanistically BV increased lung macrophages 10 days after treatment and enhanced antigen presenting molecules within the lung. To determine if an increased amount of macrophages is part of the protection observed in BV treated animals we transplanted lung macrophages from healthy animals into recipient mice. Indeed, mice that received a macrophage cell transplant showed reduced viral load at day 4 of MCoV infection. In addition, we also found the observed reduction of interferon pathway genes. Overall, we conclude that BV enhances viral clearance and lung integrity by increasing lung macrophages leading to enhanced coronavirus clearance and reduced lung apoptosis.