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Publications

Journal Article Research Support, N.I.H., Intramural Epublish 26 citations

PubMed: 38086794 DOI: 10.1038/s41467-023-43447-0

Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2.

Nat Commun 14(1):8229

Authors: Kerry L Hilligan, Sivaranjani Namasivayam, Chad S Clancy, Paul J Baker, Samuel I Old, Victoria Peluf, Eduardo P Amaral, Sandra D Oland, Danielle O'Mard, Julie Laux, Melanie Cohen, Nicole L Garza, Bernard A P Lafont, Reed F Johnson, Carl G Feng, Dragana Jankovic, Olivier Lamiable, Katrin D Mayer-Barber, Alan Sher

Affiliations

  • Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Malaghan Institute of Medical Research, Wellington, 6012, New Zealand.
  • Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
  • Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Malaghan Institute of Medical Research, Wellington, 6012, New Zealand.
  • Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. Immunoparasitology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Flow Cytometry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • SARS-CoV2- Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Immunology and Host Defense Group, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2006, Australia.
  • Centenary Institute, The University of Sydney, Camperdown, NSW, 2050, Australia.
  • Immunoparasitology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Abstract

Type-1 and type-3 interferons (IFNs) are important for control of viral replication; however, less is known about the role of Type-2 IFN (IFNγ) in anti-viral immunity. We previously observed that lung infection with Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 in mice yet drives low levels of type-1 IFNs but robust IFNγ. Here we examine the role of ongoing IFNγ responses to pre-established bacterial infection on SARS-CoV-2 disease outcomes in two murine models. We report that IFNγ is required for iv BCG induced reduction in pulmonary viral loads, an outcome dependent on IFNγ receptor expression by non-hematopoietic cells. Importantly, we show that BCG infection prompts pulmonary epithelial cells to upregulate IFN-stimulated genes with reported anti-viral activity in an IFNγ-dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirm the anti-viral properties of IFNγ by demonstrating that the recombinant cytokine itself provides strong protection against SARS-CoV-2 challenge when administered intranasally. Together, our data show that a pre-established IFNγ response within the lung is protective against SARS-CoV-2 infection, suggesting that concurrent or recent infections that drive IFNγ may limit the pathogenesis of SARS-CoV-2 and supporting possible prophylactic uses of IFNγ in COVID-19 management.

MeSH

Interferon-Gamma, Cells, Genes, Sars-Cov-2, Lung, Biological Science Disciplines, Covid-19, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections

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