Maternal helminth infection promotes offspring long-term antiviral immunity via microbiota 3855

Abstract Description Early-life microbiota exposures are crucial for lifelong health. While the effects of antibiotics and processed diets on microbiota are well-studied, the evolutionary role of helminth-altered microbiota is often neglected. Mammals, except humans in high- and middle-income societies over the past century, co-evolved with helminths. These organisms shape microbiota and immunity, but the impact of their absence in modern human health, especially during early development, remains poorly understood. To address this, we developed a maternal helminth infection model using Heligmosomoides polygyrus. Bulk RNA sequencing revealed maternal helminth infection activated type I interferon and antiviral pathways in offspring lung epithelium. This maternal-restricted infection provided lasting protection against respiratory syncytial virus and influenza in offspring. Cross-fostering and antibiotics treatment showed maternal helminth infection enhances lung antiviral immunity during the nurturing period in a microbiota-dependent manner. Transfer cecal microbiota to germ-free mice conferred long-term protection and serum from these microbiota-recipient mice induced interferon in lung epithelium. Using mass spectrometry and metagenomics, our ongoing work aims to identify microbiota components driving antiviral response. These findings offer insights into helminth-microbiota-host interactions and strategies to promote early-life antiviral immunity without reintroducing helminths to humans. Funding Sources Supported by the Branco Weiss Fellowship—Society in Science; Searle Scholars Program; Pew Latin Ammerican Fellowship - The Pew Charitable Trusts Topic Categories Mucosal and Regional Immunology (MUC)