A history of helminth exposure protects against pneumovirus infection in an IL-4Rα-independent manner

Helminths have developed a reputation for being able to regulate bystander inflammatory disorders and the mechanisms for how they carry this out are beginning to be elucidated. In this study, we investigated the impact of helminth infection on immune control in a model of lethal viral pneumonia. BALB/c mice were infected with Nippostrongylus brasiliensis, and at either 6 or 35 days after N. brasiliensis infection, mice were intranasally infected with a wild-type pneumonia virus of mice (PVM, strain J3666) or a recombinant virus expressing the luciferase gene (PVM-luc) to track viral replication over time by in vivo imaging. PVM belongs to the Pneumoviridae family and is a murine model for the closely related human respiratory syncytial respiratory virus (hRSV), a respiratory virus of medical significance in neonates, geriatrics, and immunosuppressed patients. Based on daily weight changes and viral bioluminescence, we demonstrated that prior exposure to helminths protects against PVM-induced pathology compared to naïve PVM-infected mice that exhibit a deleterious phenotype. Interestingly, protection was independent of IL-4Rα signaling, as both wild-type and IL-4Rα-/- mice were equally protected after helminth exposure. N. brasiliensis-induced protection was abolished by high doses of PVM-luc, which indicated a fine threshold for protection. Further investigations are needed to determine how exposure to N. brasiliensis can control viral replication and/or regulate PVM-associated detrimental inflammation.