Innate immune cells play pivotal role in severe neonatal influenza pathogenesis 3783

Abstract Description Children, especially the youngest, are highly vulnerable to influenza with increased rates of disease and mortality compared to non-elderly adults. Research indicates that neonatal antiviral responses differ significantly from adults due to variations in their immune responses, highlighting the need for targeted therapies. Our study investigated the differences in influenza pathogenesis between neonatal (5 days old) and adult (8-16 weeks old) wild-type C57BL/6 mice using an inhalational infection model that more strongly mimics natural virus transmission than traditional intranasal inoculations. Neonates exhibited increased mortality to severe influenza challenge even when dosing was 50 times less than that for adult animals. Neonatal viral titers, local cytokine production, and lung damage on histological examination was also demonstrated. We found a notable elevation of innate immune cells in neonatal infected lungs, particularly monocytes and neutrophils. These monocytes and neutrophils were sorted by flow cytometry, and RNA sequencing revealed numerous differential pathways associated with the increased pathogenesis of influenza in neonates. Most prominently, there were differences in Toll-like receptor expression and interferon stimulated pathways. Future mechanistic experiments utilizing genetic mice models and state of the art spatial analysis will provide further insights into the age-dependent susceptibility to influenza. Funding Sources Burroughs Wellcome Fund Topic Categories Viral Immunology (VIR)