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

McFarlane, A. J. et al. (2017) Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota. Journal of Allergy and Clinical Immunology, 140(4), 1068-1078.e6. (doi: 10.1016/j.jaci.2017.01.016) (PMID:28196762) (PMCID:PMC6485385)

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Abstract

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.

Item Type:Articles
Additional Information:Supported by grants MRC DTA 2009-2013 G09000184-2/1, MRC DTA 2010-2014 G1000388-1/1, and MRC MR/L008394/1. D.J.D. was supported by a Medical Research Council Senior Non-clinical Fellowship (G1002046).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maizels, Professor Rick
Authors: McFarlane, A. J., McSorley, H. J., Davidson, D. J., Fitch, P. M., Errington, C., Mackenzie, K. J., Gollwitzer, E. S., Johnston, C. J.C., MacDonald, A. S., Edwards, M. R., Harris, N. L., Marsland, B. J., Maizels, R. M., and Schwarze, J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Allergy and Clinical Immunology
Publisher:Elsevier
ISSN:0091-6749
ISSN (Online):1097-6825
Published Online:11 February 2017
Copyright Holders:Copyright © 2017 American Academy of Allergy, Asthma and Immunology
First Published:First published in Journal of Allergy and Clinical Immunology 140(4):1068-1078.e6
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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