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| Status |
Public on Nov 01, 2023 |
| Title |
Pre-existing interferon gamma conditions the lung to mediate early control of SARS-CoV-2 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Interferons (IFNs) are critical for anti-viral host defence. Type-1 and type-3 IFNs are typically associated with early control of viral replication and promotion of inflammatory immune responses; however, less is known about the role of IFNγ in anti-viral immunity, particularly in the context of SARS-CoV-2. We have previously observed that lung infection with attenuated bacteria M. bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 (SCV2) infection and disease in two mouse models. Assessment of the pulmonary cytokine milieu revealed that iv BCG induces a robust IFNγ response and low levels of IFNβ. Here we examined the role of ongoing IFNγ responses due to concurrent bacterial infection on SCV2 disease outcomes in two murine models. We report that IFNγ is required for iv BCG induced reduction in pulmonary viral loads and that this outcome is dependent on IFNγ receptor expression by non-hematopoietic cells. Further analysis revealed that BCG infection promotes the upregulation of ISGs with reported anti-viral activity by pneumocytes and bronchial epithelial cells in an IFNγ dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirmed the importance of IFNγ in these anti-viral effects by demonstrating that the recombinant cytokine itself provides strong protection against SCV2 challenge when administered intranasally. Together, our data show that a pre-established IFNγ response within the lung is protective against SCV2 infection, suggesting that concurrent or recent infections that drive IFNγ may limit the pathogenesis of this virus and supporting possible prophylactic uses of this cytokine in COVID-19 management.
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| Overall design |
PBS iv, BCG iv inoculated mice as well as each group administred anti-IFNγ were infected with SARS-CoV-2 via the intra-nasal route. Lungs were harvested from the mice 3 days post infection and single cell suspenions were generated for scRNAseq analysis
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| Citation(s) |
38086794 |
| |
| Submission date |
Jul 05, 2023 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Sivaranjani Namasivayam |
| E-mail(s) |
sivaranjani.namasivayam@nih.gov
|
| Organization name |
NIH
|
| Department |
NIAID
|
| Street address |
33 North Drive
|
| City |
Bethesda |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA991639 |
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