Paternal immune activation protects offspring from severe disease during viral infection 3329

Abstract Description Maternal immune activation during gestation can influence offspring behavior and immunity. However, the influence of paternal immune activation (PIA) on progeny is understudied. Limited evidence indicates that PIA influences offspring behavior via alterations in epigenetic information carried within sperm. Yet, explorations into the impacts of PIA on offspring immunity are minimal. I have shown that PIA with or without viral replication remodels the epigenetic information within sperm by altering the small RNA profile. Moreover, we have demonstrated that PIA alters transcription in the early embryo, downregulating immune regulatory genes. To further explore the impacts of PIA, juvenile offspring from PIA or control males were infected with an adult lethal dose of Influenza A Virus. Offspring sired by PIA males had improved survival and less severe clinical outcomes during infection. Protection did not correlate with lower viral burden in the lungs, leading us to explore differences in immune mediated pathology. Altogether, inflammation in the father alters offspring immunity, providing protection during viral infection. We believe PIA mediated alterations to sperm small RNAs spark differential immune regulation as early as the preimplantation embryo, leading to protection from severe infection within offspring. This paradigm-altering finding uncovers a new mechanism in the evolutionary arms race between host and pathogen wherein immunity can be acquired within one generation. Funding Sources NSF GRFP The PEW Charitable Trust The David and Lucille Packard Foundation Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)