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

Amanda J. McFarlane, Henry J. McSorley, Donald J. Davidson, Paul M. Fitch, Claire Errington, Karen J. Mackenzie, Eva S. Gollwitzer, Chris J.C. Johnston, Andrew S. MacDonald, Michael R. Edwards, Nicola L. Harris, Benjamin J. Marsland, Rick M. Maizels, Jürgen Schwarze

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1068-1078.e6
JournalJournal of Allergy and Clinical Immunology
Volume140
Issue number4
DOIs
Publication statusPublished - 1 Oct 2017
Externally publishedYes

Keywords

  • Heligmosomoides polygyrus
  • helminths
  • microbiome
  • Respiratory syncytial virus
  • type I interferon

Cite this

McFarlane, A. J., McSorley, H. J., Davidson, D. J., Fitch, P. M., Errington, C., Mackenzie, K. J., ... Schwarze, J. (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. https://doi.org/10.1016/j.jaci.2017.01.016
McFarlane, Amanda J. ; McSorley, Henry J. ; Davidson, Donald J. ; Fitch, Paul M. ; Errington, Claire ; Mackenzie, Karen J. ; Gollwitzer, Eva S. ; Johnston, Chris J.C. ; MacDonald, Andrew S. ; Edwards, Michael R. ; Harris, Nicola L. ; Marsland, Benjamin J. ; Maizels, Rick M. ; Schwarze, Jürgen. / Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota. In: Journal of Allergy and Clinical Immunology. 2017 ; Vol. 140, No. 4. pp. 1068-1078.e6.
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title = "Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota",
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.",
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author = "McFarlane, {Amanda J.} and McSorley, {Henry J.} and Davidson, {Donald J.} and Fitch, {Paul M.} and Claire Errington and Mackenzie, {Karen J.} and Gollwitzer, {Eva S.} and Johnston, {Chris J.C.} and MacDonald, {Andrew S.} and Edwards, {Michael R.} and Harris, {Nicola L.} and Marsland, {Benjamin J.} and Maizels, {Rick M.} and J{\"u}rgen Schwarze",
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McFarlane, AJ, McSorley, HJ, Davidson, DJ, Fitch, PM, Errington, C, Mackenzie, KJ, Gollwitzer, ES, Johnston, CJC, MacDonald, AS, Edwards, MR, Harris, NL, Marsland, BJ, Maizels, RM & Schwarze, J 2017, 'Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota' Journal of Allergy and Clinical Immunology, vol. 140, no. 4, pp. 1068-1078.e6. https://doi.org/10.1016/j.jaci.2017.01.016

Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota. / McFarlane, Amanda J.; McSorley, Henry J.; Davidson, Donald J.; Fitch, Paul M.; Errington, Claire; Mackenzie, Karen J.; Gollwitzer, Eva S.; Johnston, Chris J.C.; MacDonald, Andrew S.; Edwards, Michael R.; Harris, Nicola L.; Marsland, Benjamin J.; Maizels, Rick M.; Schwarze, Jürgen.

In: Journal of Allergy and Clinical Immunology, Vol. 140, No. 4, 01.10.2017, p. 1068-1078.e6.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota

AU - McFarlane, Amanda J.

AU - McSorley, Henry J.

AU - Davidson, Donald J.

AU - Fitch, Paul M.

AU - Errington, Claire

AU - Mackenzie, Karen J.

AU - Gollwitzer, Eva S.

AU - Johnston, Chris J.C.

AU - MacDonald, Andrew S.

AU - Edwards, Michael R.

AU - Harris, Nicola L.

AU - Marsland, Benjamin J.

AU - Maizels, Rick M.

AU - Schwarze, Jürgen

PY - 2017/10/1

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N2 - 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.

AB - 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.

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