Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion
- Cardiff University, United Kingdom
- University of Glasgow, United Kingdom
- University of Edinburgh, United Kingdom
- MRC Laboratory of Molecular Biology, United Kingdom
Abstract
Interleukin 25 (IL-25) is a major 'alarmin' cytokine, capable of initiating and amplifying the type 2 immune response to helminth parasites. However its role in the later effector phase of clearing chronic infection remains unclear. The helminth Heligmosomoides polygyrus establishes long-term infections in susceptible C57BL/6 mice, but is slowly expelled in BALB/c mice from day 14 onwards. We noted that IL-25R (Il17rb)-deficient BALB/c mice were unable to expel parasites despite type 2 immune activation comparable to the wild-type. We then established that in C57BL/6 mice, IL-25 adminstered late in infection (days 14-17) drove immunity. Moreover when IL-25 and IL-4 were delivered to Rag1-deficient mice, the combination resulted in near complete expulsion of the parasite, even following administration of an anti-CD90 antibody to deplete innate lymphoid cells (ILCs). Hence, effective anti-helminth immunity during chronic infection requires an innate effector cell population that is synergistically activated by the combination of IL-4Rα and IL-25R signaling.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
Wellcome (106122)
- Rick M Maizels
Wellcome (90281)
- Rick M Maizels
European Commission (657639)
- Katherine A Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal protocols adhered to the guidelines of the UK home office and complied with the Animals (Scientific Procedures) Act 1986. The protocols were approved by the Ethical Review Committees of the University of Edinburgh (UK Home Office Project number 60/4105) and the University of Glasgow (Project number 70/8384).
Copyright
© 2018, Smith et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion
eLife 7:e38269.
https://doi.org/10.7554/eLife.38269
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