Coronavirus activates a 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 altruistic defense mechanism to protect their niche. Here, we provide preliminary data on the altruistic stem cell (ASC) based defense against a mouse corona virus; MHV-1 infection. In a mouse model of mesenchymal stem cell (MSC) mediated M. tuberculosis (Mtb) dormancy, MHV-1 infection in the lung exhibited 20 fold lower viral loads than the healthy control mice, suggesting the potential enhancement of an anti-MHV-1 defense by Mtb. This defense involved the in vivo expansion and reprogramming of CD271+ MSCs in the lung to ASC phenotype characterized by activation of genes involved in the HIF-2alpha stemness pathway. The conditioned media of the ASCs exhibited direct anti-viral activity in an in vitro model of MHV-1 induced toxicity to type II alveolar epithelial cells. MHV-1 infected Mtb harboring group versus MHV-1 alone groupexhibited an 8-fold (p<0.02; n=4) higher ASC reprogramming and 5-fold (p<0.001; n=3, student t test) higher anti-viral activity. However, ASCs facilitated intracellular replication and extracellular release of Mtb. Thus, our data suggest that MSCs exert an innate defense against MHV-1 by activating the ASC defense mechanism, which might be exploited by dormant Mtb to undergo reactivation. Hence, our findings may provide a novel anti-viral defense mechanism against novel corona virus SARS-Cov2, which could be further utilized to develop vaccine

Initiation of Post-Primary Tuberculosis of the Lungs: Exploring the Secret Role of Bone Marrow Derived Stem Cells

“…These findings raise human bone marrow derived stem cells as the site of Mtb latency ( 27 ). Recently, we have shown that stem cell altruism may be involved in Mtb -reactivation ( 28 ), and in the aerosol-induced immunity ( 29 ). These recent studies indicate the emerging role of BM stem cell niche in the pathogenesis and community transmission of Mtb .…”

Concurrent tuberculosis and COVID-19: reports of three cases

“…It has been postulated that corona virus may activate a stem cell mediated defense mechanism, that accentuates activation of dormant TB. 5 Use of immune-modulators in moderate and severe COVID-19, as steroids and tocilizumab, may also lead to reactivation of latent TB in high TB burden country like ours. Concomitant use of anti-TB chemotherapy may also lead to drug-drug interaction and additive hepatotoxicity, if remdesivir has been used for treatment of COVID-19.…”

Peculiarities of tuberculosis in the COVID‑19 pandemic

“…As most TB in young children is acquired in their own household, social distancing measures that keep a family together for long periods of time are likely to result in more exposure of children to infectious TB index cases. Contact screening for COVID-19 should therefore include questions about TB in the household in order to protect young children from additional risks [11].…”