Enteric helminth-induced type-I interferon signalling protects against pulmonary virus infection through interaction with the microbiota

BACKGROUND: Helminth parasites have been reported to have beneficial immune modulatory effects in allergic and autoimmune conditions and detrimental consequences in tuberculosis and some viral infections. Their role in co-infection with respiratory viruses is not clear.

OBJECTIVE: Here, we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model.

METHODS: A murine helminth/ RSV co-infection model was developed. Mice were infected by oral gavage with 200 stage 3 H. polygyrus larvae. 10 days later, mice were infected with either RSV or UV-inactivated RSV (UV-RSV) intranasally.

RESULTS: H. polygyrus infected mice showed significantly less disease and pulmonary inflammation after RSV infection, associated with reduced viral load. Adaptive immune responses including Th2 responses were not essential since protection against RSV was maintained in RAG1(-/-) and IL-4Rα(-/-) mice. Importantly, H. polygyrus infection upregulated expression of type I IFNs and IFN stimulated genes (ISG) in both the duodenum and the lung, and its protective effects were lost in both IFNAR1(-/-) and germ-free mice, revealing essential roles for type I IFN signalling and microbiota in H. polygyrus induced protection against RSV.

CONCLUSION: These data demonstrate that a strictly enteric helminth infection can have remote protective antiviral effects in the lung through induction of a microbiota-dependent type I IFN response.