Coronavirus activates an altruistic stem cell mediated defense mechanism that reactivates dormant tuberculosis: implications in COVID-19 pandemic.

ABSTRACT We postulate that similar to bacteria, adult stem cells may also exhibit an altruistic defense mechanism to protect their niche against external threat. Here, we report mesenchymal stem cell (MSC) based altruistic defense against a mouse model of coronavirus, murine hepatitis virus-1 (MHV-1) infection of lung. MHV-1 infection led to reprogramming of CD271+MSCs in the lung to an “enhanced stemness” phenotype that exhibits altruistic behavior as per our previous work in human embryonic stem cells. The reprogrammed MSCs exhibited transient expansion for two weeks followed by apoptosis, and expression of stemness genes The conditioned media of the reprogrammed MSCs exhibited direct anti-viral activity in an in vitro model of MHV-1 induced toxicity to type II alveolar epithelial cells by increasing their survival/proliferation and decreasing viral load. Thus, the reprogrammed MSCs can be identified as altruistic stem cells (ASCs) which exert a unique altruistic defense against MHV-1. In a mouse model of MSC mediated Mycobacterium tuberculosis (Mtb) dormancy, MHV-1 infection in the lung exhibited 20-fold lower viral loads than the Mtb-free control mice on the third week of viral infection, and also exhibited 6-fold increase of ASCs, thereby enhancing the altruistic defense. Notably, these ASCs exhibited intracellular replication of Mtb, and their extracellular release. Animals showed TB reactivation suggesting that dMtb may exploit ASCs for disease reactivation..