Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection.
<h4>Background</h4>Type III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is kn...
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2021
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oai:doaj.org-article:164f797b44ad4746969acad593a6ba442021-12-02T20:13:48ZMurine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection.1932-620310.1371/journal.pone.0255309https://doaj.org/article/164f797b44ad4746969acad593a6ba442021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255309https://doaj.org/toc/1932-6203<h4>Background</h4>Type III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNλ genes affect influenza responses, but the effect of IFNλ subtypes on bacterial super-infection is unknown.<h4>Methods</h4>Using an established model of influenza, Staphylococcus aureus super-infection, we studied IFNλ3-/- and control mice to model a physiologically relevant reduction in IFNλ and to address its role in super-infection.<h4>Results</h4>Surprisingly, IFNλ3-/- mice did not have significantly lower total IFNλ than co-housed controls, and displayed no change in viral or bacterial clearance. Importantly, both control and IFNλ3-/- mice displayed a positive correlation between viral burden and total IFNλ in the bronchoalveolar lavage during influenza/bacterial super-infection, suggesting that higher influenza viral burden drives a similar total IFNλ response regardless of IFNλ3 gene integrity. Interestingly, total IFNλ levels positively correlated with bacterial burden, while viral burden and bronchoalveolar lavage cellularity did not.<h4>Conclusions</h4>These data suggest IFNλ2 can compensate for IFNλ3 to mount an effective antiviral and defense, revealing a functional redundancy in these highly similar IFNλ subtypes. Further, the IFNλ response to influenza, as opposed to changes in cellular inflammation or viral load, significantly correlates with susceptibility to bacterial super-infection. Moreover, the IFNλ response is regulated and involves redundant subtypes, suggesting it is of high importance to pulmonary pathogen defense.Helen E RichDanielle AntosCollin C McCourtWen Quan ZhengLouis J DevitoKevin J McHughRadha GopalJieru WangJohn F AlcornPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0255309 (2021) |
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Medicine R Science Q Helen E Rich Danielle Antos Collin C McCourt Wen Quan Zheng Louis J Devito Kevin J McHugh Radha Gopal Jieru Wang John F Alcorn Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. |
| description |
<h4>Background</h4>Type III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNλ genes affect influenza responses, but the effect of IFNλ subtypes on bacterial super-infection is unknown.<h4>Methods</h4>Using an established model of influenza, Staphylococcus aureus super-infection, we studied IFNλ3-/- and control mice to model a physiologically relevant reduction in IFNλ and to address its role in super-infection.<h4>Results</h4>Surprisingly, IFNλ3-/- mice did not have significantly lower total IFNλ than co-housed controls, and displayed no change in viral or bacterial clearance. Importantly, both control and IFNλ3-/- mice displayed a positive correlation between viral burden and total IFNλ in the bronchoalveolar lavage during influenza/bacterial super-infection, suggesting that higher influenza viral burden drives a similar total IFNλ response regardless of IFNλ3 gene integrity. Interestingly, total IFNλ levels positively correlated with bacterial burden, while viral burden and bronchoalveolar lavage cellularity did not.<h4>Conclusions</h4>These data suggest IFNλ2 can compensate for IFNλ3 to mount an effective antiviral and defense, revealing a functional redundancy in these highly similar IFNλ subtypes. Further, the IFNλ response to influenza, as opposed to changes in cellular inflammation or viral load, significantly correlates with susceptibility to bacterial super-infection. Moreover, the IFNλ response is regulated and involves redundant subtypes, suggesting it is of high importance to pulmonary pathogen defense. |
| format |
article |
| author |
Helen E Rich Danielle Antos Collin C McCourt Wen Quan Zheng Louis J Devito Kevin J McHugh Radha Gopal Jieru Wang John F Alcorn |
| author_facet |
Helen E Rich Danielle Antos Collin C McCourt Wen Quan Zheng Louis J Devito Kevin J McHugh Radha Gopal Jieru Wang John F Alcorn |
| author_sort |
Helen E Rich |
| title |
Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. |
| title_short |
Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. |
| title_full |
Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. |
| title_fullStr |
Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. |
| title_full_unstemmed |
Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. |
| title_sort |
murine type iii interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/164f797b44ad4746969acad593a6ba44 |
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