| First Author | Hilligan KL | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 8229 |
| PubMed ID | 38086794 | Mgi Jnum | J:343550 |
| Mgi Id | MGI:7566745 | Doi | 10.1038/s41467-023-43447-0 |
| Citation | Hilligan KL, et al. (2023) Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2. Nat Commun 14(1):8229 |
| abstractText | 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 (IFNgamma) 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 IFNgamma. Here we examine the role of ongoing IFNgamma responses to pre-established bacterial infection on SARS-CoV-2 disease outcomes in two murine models. We report that IFNgamma is required for iv BCG induced reduction in pulmonary viral loads, an outcome dependent on IFNgamma 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 IFNgamma-dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirm the anti-viral properties of IFNgamma 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 IFNgamma response within the lung is protective against SARS-CoV-2 infection, suggesting that concurrent or recent infections that drive IFNgamma may limit the pathogenesis of SARS-CoV-2 and supporting possible prophylactic uses of IFNgamma in COVID-19 management. |
