Maternal Helminths Rewire the Microbiota to Promote Offspring Antiviral Immunity via Indole-3-Propionic Acid

Yet, the role of helminths, mammals’ symbiotic evolutionary partners that have been eliminated from modern societies, remains poorly understood. Here, we show that maternal helminth infection enhances type I interferon (IFN-I) signaling in the offspring’s lung epithelium, conferring broad and lasting protection against respiratory viruses.

Using cross-fostering, antibiotics, and gnotobiotic systems, we demonstrate that this antiviral immunity is mediated by helminth-altered maternal microbiota. Mechanistically, we identify the microbial tryptophan metabolite indole-3-propionic acid (IPA) as a key driver of IFN-I responses in lung epithelium. Furthermore, the tryptophan metabolic pathway is enriched in the microbiome of helminth-infected human populations, and IPA alone is sufficient to enhance IFN-I signaling in human bronchial epithelial cells.