Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection

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 speci...

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Published in:PloS one 2021-10, Vol.16 (10), p.e0255309-e0255309
Main Authors: Rich, Helen E, Antos, Danielle, McCourt, Collin C, Zheng, Wen Quan, Devito, Louis J, McHugh, Kevin J, Gopal, Radha, Wang, Jieru, Alcorn, John F
Format: Article
Language:English
Subjects:
Alveoli
Analysis
Animals
Antiviral agents
Bacteria
Biology and Life Sciences
Bronchus
Cell Line
Coinfection - immunology
Coinfection - microbiology
Correlation
Cytokines
Disease susceptibility
Dogs
Evaluation
Experiments
Families & family life
Female
Genetic aspects
Genetic polymorphisms
Health aspects
Immunology
Infections
Influenza
Interferon
Interferons - analysis
Interferons - genetics
Interferons - immunology
Interleukins - genetics
Interleukins - immunology
Lavage
Lungs
Madin Darby Canine Kidney Cells
Male
Medical research
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - pathology
Pandemics
Pathogens
Pediatrics
Polymorphism, Genetic - genetics
Proteins
Redundancy
Research and Analysis Methods
Staphylococcal Infections - immunology
Staphylococcal Infections - prevention & control
Staphylococcus aureus
Staphylococcus aureus - immunology
Staphylococcus infections
Streptococcus infections
Superinfection
Superinfection - immunology
Superinfection - microbiology
Viral Load - immunology
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cited_by cdi_FETCH-LOGICAL-c692t-a60169dc6777effcd67ce07410997e301c58e5ed45d55624e590f8f2a541805d3
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creator Rich, Helen E
Antos, Danielle
McCourt, Collin C
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Devito, Louis J
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Gopal, Radha
Wang, Jieru
Alcorn, John F
description 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. 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. 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. 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.
doi_str_mv 10.1371/journal.pone.0255309
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Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>ProQuest Publicly Available Content database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rich, Helen E</au><au>Antos, Danielle</au><au>McCourt, Collin C</au><au>Zheng, Wen Quan</au><au>Devito, Louis J</au><au>McHugh, Kevin J</au><au>Gopal, Radha</au><au>Wang, Jieru</au><au>Alcorn, John F</au><au>Harrod, Kevin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-10-07</date><risdate>2021</risdate><volume>16</volume><issue>10</issue><spage>e0255309</spage><epage>e0255309</epage><pages>e0255309-e0255309</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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. 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. 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. 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34618816</pmid><doi>10.1371/journal.pone.0255309</doi><tpages>e0255309</tpages><orcidid>https://orcid.org/0000-0001-5997-7711</orcidid><orcidid>https://orcid.org/0000-0002-8451-0600</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2021-10, Vol.16 (10), p.e0255309-e0255309
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_2580000250
source PubMed Central; ProQuest Publicly Available Content database
subjects Alveoli
Analysis
Animals
Antiviral agents
Bacteria
Biology and Life Sciences
Bronchus
Cell Line
Coinfection - immunology
Coinfection - microbiology
Correlation
Cytokines
Disease susceptibility
Dogs
Evaluation
Experiments
Families & family life
Female
Genetic aspects
Genetic polymorphisms
Health aspects
Immunology
Infections
Influenza
Interferon
Interferons - analysis
Interferons - genetics
Interferons - immunology
Interleukins - genetics
Interleukins - immunology
Lavage
Lungs
Madin Darby Canine Kidney Cells
Male
Medical research
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - pathology
Pandemics
Pathogens
Pediatrics
Polymorphism, Genetic - genetics
Proteins
Redundancy
Research and Analysis Methods
Staphylococcal Infections - immunology
Staphylococcal Infections - prevention & control
Staphylococcus aureus
Staphylococcus aureus - immunology
Staphylococcus infections
Streptococcus infections
Superinfection
Superinfection - immunology
Superinfection - microbiology
Viral Load - immunology
title Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection
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