학술논문
Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2
Document Type
article
Author
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
Source
Nature Communications, Vol 14, Iss 1, Pp 1-16 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
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.