IL-36γ prevents immunopathology during influenza infection

Autor: Alexander N Wein, Paul Dunbar, Sean R McMaster, Nivedha Kumar, Sarah L Hayward, Timothy L Denning, Jacob E Kohlmeier
Rok vydání: 2017
Předmět:
Zdroj: The Journal of Immunology. 198:148.2-148.2
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.198.supp.148.2
Popis: Influenza infection is a disease of high importance for public health, but the roles of individual cytokines in the pathogenesis of influenza infection remains to be elucidated. The IL-36 cytokine family is a relative of IL-1 and functions and signals in an analogous fashion. Despite their roles in many inflammatory conditions, the impact of IL-36 family cytokines on influenza pathogenesis and immunity remain largely undefined. To better understand the roles of IL-36 cytokines during influenza infection, we investigated IL-36 cytokine expression during low (x31) and high (PR8) pathogenesis influenza infection. We observed that IL-36γ is significantly upregulated during both low (x31) and high (PR8) pathogenesis influenza infection and has immune and non-immune cell sources. Unexpectedly, we observed that deletion of IL-36γ causes greater morbidity and mortality compared to WT mice, suggesting that the IL-36γ has a previously unknown protective function in addition to its pro-inflammatory roles. This increased morbidity correlates with a significant decrease in the number of alveolar macrophages in IL-36γ−/− mice during the early stages of influenza infection, and the rate of viral clearance varies between the WT and IL-36γ−/− mice based on the strain and dose of virus. We are currently performing RNA-Seq analysis to identify the protective immune mechanisms induced by IL-36γ signaling during highly pathogenic influenza infection. Overall, our results suggest a novel, protective role for IL-36γ during influenza infection and may suggest potential therapeutic approaches for ameliorating influenza pathogenesis.
Databáze: OpenAIRE
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