Poster L13 - A Comprehensive Study of Influenza Pathogenesis in Juvenile Mice: A Multidimensional Approach

Introduction: Influenza infections pose significant public health challenges globally, particularly among children for whom pneumonia remains a leading cause of mortality. Despite advancements, reliable biomarkers predicting severe pediatric influenza are lacking and it is unclear as to why some juveniles may experience severe disease and not others. This study aims to elucidate molecular pathways and biomarkers associated with influenza severity in genetically diverse juvenile animals, providing insights crucial for pediatric clinical management and intervention strategies.

Materials and

Methods: We characterized the immunological responses to influenza in young Jackson Laboratories Diversity Outbred (JDO) mice. The data collected includes cell counts (via flow cytometry), lung cytokine concentrations, and metabolomics to identify biomarkers correlating with severe disease phenotypes. Animal behavior, viral load, and lung hysteresis were used to classify each infection as severe or mild. Multidimensional clustering analysis (PCA and UMAP) was used to determine if the lung immunologic data clustered meaningfully with the severity labels. We will next analyze this data with machine learning algorithms to discern potential biomarkers. This endeavor seeks to uncover new biomarkers, molecular targets, and pathways relevant to pneumonia severity.

Results, Conclusions, and Discussions: Preliminary analysis of the measured data indicates noticeable distinctions in cytokine profiles between male and female juvenile mice. Particularly evident at 5 days post infection, these differences in immune response appear to intensify over time. Concurrently, analysis of myeloid and lymphoid cell counts supports this observation, with the most significant differences between sexes emerging during the 5-day period post-infection. Principle Component Analysis reinforces these disparities, suggesting the presence of distinct sex-specific immune response patterns in juvenile mice following influenza infection.

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