Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion

Smith, K. A., Loser, S., Varyani, F., Harcus, Y., McSorley, H. J., McKenzie, A. N.J. and Maizels, R. (2018) Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion. eLife, 7, e38269. (doi: 10.7554/eLife.38269) (PMID:30238872) (PMCID:PMC6173579)

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Abstract

Interleukin 25 (IL-25) is a major 'alarmin' cytokine, capable of initiating and amplifying the type 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maizels, Professor Rick
Creator Roles:
Maizels, R.Conceptualization, Funding acquisition, Project administration, Supervision, Writing – original draft, Writing – review and editing
Authors: Smith, K. A., Loser, S., Varyani, F., Harcus, Y., McSorley, H. J., McKenzie, A. N.J., and Maizels, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in eLife
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
765221Helminths and the Immune System: Regulation, Regulators and ImmunityRichard MaizelsWellcome Trust (WELLCOTR)106122/A/14/ZIII - PARASITOLOGY