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Coronavirus Activates an Altruistic Stem Cell-Mediated Defense Mechanism that Reactivates Dormant Tuberculosis: Implications in Coronavirus Disease 2019 Pandemic.

Authors
  • Pathak, Lekhika1
  • Gayan, Sukanya1
  • Pal, Bidisha2
  • Talukdar, Joyeeta1
  • Bhuyan, Seema1
  • Sandhya, Sorra1
  • Yeger, Herman3
  • Baishya, Debabrat4
  • Das, Bikul5
  • 1 Department of Stem Cell and Infectious Diseases, KaviKrishna Laboratory, Guwahati Biotech Park, Indian Institute of Technology, Guwahati, India. , (India)
  • 2 Department of Stem Cell and Infectious Diseases, KaviKrishna Laboratory, Guwahati Biotech Park, Indian Institute of Technology, Guwahati, India; Department of Stem Cell and Infection, Thoreau Lab for Global Health, University of Massachusetts, Lowell, Massachusetts. , (India)
  • 3 Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada. , (Canada)
  • 4 Department of Stem Cell and Infectious Diseases, KaviKrishna Laboratory, Guwahati Biotech Park, Indian Institute of Technology, Guwahati, India; Department of Bioengineering and Technology, Gauhati University, Guwahati, India. , (India)
  • 5 Department of Stem Cell and Infectious Diseases, KaviKrishna Laboratory, Guwahati Biotech Park, Indian Institute of Technology, Guwahati, India; Department of Stem Cell and Infection, Thoreau Lab for Global Health, University of Massachusetts, Lowell, Massachusetts. Electronic address: [email protected] , (India)
Type
Published Article
Journal
American Journal Of Pathology
Publisher
Elsevier
Publication Date
Apr 19, 2021
Identifiers
DOI: 10.1016/j.ajpath.2021.03.011
PMID: 33887214
Source
Medline
Language
English
License
Unknown

Abstract

We postulate that similar to bacteria, adult stem cells may also exhibit an altruistic defense mechanism to protect their niche against external threat. Herein, 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 previous work in human embryonic stem cells. The reprogrammed MSCs exhibited transient expansion for 2 weeks, followed by apoptosis and expression of stemness genes. The conditioned media of the reprogrammed MSCs exhibited direct antiviral 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 exhibited six-fold increase of ASCs, thereby enhancing the altruistic defense. Notably, these ASCs exhibited intracellular replication of MTB, and their extracellular release. Animals showed tuberculosis reactivation, suggesting that dormant MTB may exploit ASCs for disease reactivation. Copyright © 2021. Published by Elsevier Inc.

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