Projects per year
Abstract / Description of output
Background: Helminth parasites have been reported to have beneficial immunomodulatory effects in patients with allergic and autoimmune conditions and detrimental consequences in patients with tuberculosis and some viral infections. Their role in coinfection 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 coinfection model was developed. Mice were infected by means of oral gavage with 200 stage 3 H polygyrus larvae. Ten days later, mice were infected intranasally with either RSV or UV-inactivated RSV.
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 because protection against RSV was maintained in Rag1−/− and Il4rα−/− mice. Importantly, H polygyrus infection upregulated expression of type I interferons and interferon-stimulated genes in both the duodenum and lung, and its protective effects were lost in both Ifnar1−/− and germ-free mice, revealing essential roles for type I interferon signaling 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 interferon response.
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 coinfection model was developed. Mice were infected by means of oral gavage with 200 stage 3 H polygyrus larvae. Ten days later, mice were infected intranasally with either RSV or UV-inactivated RSV.
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 because protection against RSV was maintained in Rag1−/− and Il4rα−/− mice. Importantly, H polygyrus infection upregulated expression of type I interferons and interferon-stimulated genes in both the duodenum and lung, and its protective effects were lost in both Ifnar1−/− and germ-free mice, revealing essential roles for type I interferon signaling 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 interferon response.
Original language | English |
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Pages (from-to) | 1068-1078.e6 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 140 |
Issue number | 4 |
Early online date | 11 Feb 2017 |
DOIs | |
Publication status | Published - 1 Oct 2017 |
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Dive into the research topics of 'Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota'. Together they form a unique fingerprint.Projects
- 2 Finished
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Mechanisms of helminth induced antiviral immunity to RSV infection
Maizels, R.
1/03/14 → 28/08/17
Project: Research
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Cathelicidins as immunomodulators of host defence against infectious diseases
1/04/11 → 31/03/17
Project: Research
Profiles
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Jurgen Schwarze, FRCPCH
- Deanery of Clinical Sciences - Edward Clark Chair of Child Life and Health
- Centre for Inflammation Research
- Centre for Reproductive Health
Person: Academic: Research Active