Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection
| Autor: | Collin C. McCourt, Jieru Wang, Radha Gopal, John F. Alcorn, Kevin J. McHugh, Louis J Devito, Wen Quan Zheng, Danielle Antos, Helen E. Rich |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
RNA viruses
Male Viral Diseases medicine.medical_treatment Staphylococcus medicine.disease_cause Biochemistry Animal Diseases Madin Darby Canine Kidney Cells Interferon Lambda Mice Medical Conditions Interferon Zoonoses Medicine and Health Sciences Pathogen Immune Response Pathology and laboratory medicine Mice Knockout Multidisciplinary medicine.diagnostic_test Coinfection H1N1 virus diseases Animal Models Viral Load Medical microbiology Staphylococcal Infections Cytokine Infectious Diseases Experimental Organism Systems Staphylococcus aureus Influenza A virus Viruses Medicine Methicillin-resistant Staphylococcus aureus Swine Influenza Female medicine.symptom Pathogens Viral load medicine.drug Research Article Science Immunology Inflammation Mouse Models Biology Research and Analysis Methods Microbiology Cell Line Animal Influenza Signs and Symptoms Model Organisms Dogs Orthomyxoviridae Infections Virology medicine Influenza viruses Animals Gene Polymorphism Genetic Bacteria Interleukins Organisms Viral pathogens Biology and Life Sciences Proteins Influenza Microbial pathogens Mice Inbred C57BL Bronchoalveolar lavage Superinfection Animal Studies Bacterial pathogens Interferons Clinical Medicine Zoology Viral Transmission and Infection Orthomyxoviruses |
| Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 10, p e0255309 (2021) |
| ISSN: | 1932-6203 |
| Popis: | Background 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. Methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|