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

Smith, Katherine A. ORCID:, Löser, Stephan, Varyani, Fumi, Harcus, Yvonne, McSorley, Henry J., McKenzie, Andrew N. J. and Maizels, Rick M. 2018. Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion. eLife 7 , e38269. 10.7554/eLife.38269

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open access article under the terms of the CC-BY license.
Publisher: eLife Sciences Publications
ISSN: 2050-084X
Funders: European Commssion
Date of First Compliant Deposit: 25 September 2018
Date of Acceptance: 21 September 2018
Last Modified: 24 Oct 2022 07:32

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