| First Author | Rich HE | Year | 2021 |
| Journal | PLoS One | Volume | 16 |
| Issue | 10 | Pages | e0255309 |
| PubMed ID | 34618816 | Mgi Jnum | J:311467 |
| Mgi Id | MGI:6766501 | Doi | 10.1371/journal.pone.0255309 |
| Citation | Rich HE, et al. (2021) Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. PLoS One 16(10):e0255309 |
| abstractText | BACKGROUND: Type III interferon, or interferon lambda (IFNlambda) is a crucial antiviral cytokine induced by influenza infection. While IFNlambda is important for anti-viral host defense, published data demonstrate that IFNlambda is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNlambda genes affect influenza responses, but the effect of IFNlambda subtypes on bacterial super-infection is unknown. METHODS: Using an established model of influenza, Staphylococcus aureus super-infection, we studied IFNlambda3-/- and control mice to model a physiologically relevant reduction in IFNlambda and to address its role in super-infection. RESULTS: Surprisingly, IFNlambda3-/- mice did not have significantly lower total IFNlambda than co-housed controls, and displayed no change in viral or bacterial clearance. Importantly, both control and IFNlambda3-/- mice displayed a positive correlation between viral burden and total IFNlambda in the bronchoalveolar lavage during influenza/bacterial super-infection, suggesting that higher influenza viral burden drives a similar total IFNlambda response regardless of IFNlambda3 gene integrity. Interestingly, total IFNlambda levels positively correlated with bacterial burden, while viral burden and bronchoalveolar lavage cellularity did not. CONCLUSIONS: These data suggest IFNlambda2 can compensate for IFNlambda3 to mount an effective antiviral and defense, revealing a functional redundancy in these highly similar IFNlambda subtypes. Further, the IFNlambda response to influenza, as opposed to changes in cellular inflammation or viral load, significantly correlates with susceptibility to bacterial super-infection. Moreover, the IFNlambda response is regulated and involves redundant subtypes, suggesting it is of high importance to pulmonary pathogen defense. |
