IL-27 utilizes IRF1 for IFN-I-independent ISG expression during IAV infection of human macrophages
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Authors
Kalin, Emma
Date
2024-06-19
Type
thesis
Language
eng
Keyword
Immunology , Interleukin-27 , Innate Immunity , Influenza A Virus , Macrophages
Alternative Title
Abstract
Influenza virus (IAV) is a respiratory virus spread through aerosols or respiratory fomites causing seasonal epidemics resulting in up to 650,000 deaths annually and with the potential to cause more serious life-threatening pandemics. Recognition of IAV by host innate immune cells, such as macrophages (M), signals to activate the immune response, including key cytokines, like type I interferons (IFN-I) and the antiviral cytokine, interleukin-27 (IL-27). IFN-I signalling induces the expression of interferon-stimulated genes (ISGs), which collectively function to limit virus infection. Relatively new research has indicated a role for IL-27 in the induction of ISG expression either in an IFN- I-dependent or -independent manner. Furthermore, IL-27 has previously been shown to regulate the function of monocytes and M, including skewing M polarization towards a pro-inflammatory, M1 phenotype. However, the effects of IL-27 on polarized M during IAV infection are unknown. Therefore, we set out to characterize the relationship between IFN-I and IL-27 in the induction of ISGs in response to pandemic IAV infection (A/NY/18/2009) and to determine if IL-27 plays a role in M polarization and how this changes IAV infection. Here we show that IL-27-mediated IFN-I-independent induction of ISGs requires the presence of the transcription factor IRF1, and in the absence of IRF1, IL-27 is dependent on IFN-I to induce ISGs. As well, we show that post-infection IL-27 treatment does not confer the ability to reduce IAV infection. These results show potential correlation between IAV replication, M subtypes, and IL-27-modulation of the IFN response, allowing for a better understanding of the antiviral function of IL-27.
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This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivatives 4.0 International
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivatives 4.0 International