Thymic stromal lymphopoietin-dependent basophils promote Th2 cytokine responses following intestinal helminth infection

Paul R. Giacomin, Mark C. Siracusa, Kevin P. Walsh, Richard K. Grencis, Masato Kubo, Michael R. Comeau, David Artis

    Research output: Contribution to journalArticlepeer-review

    Abstract

    CD4+ Th2 cytokine responses promote the development of allergic inflammation and are critical for immunity to parasitic helminth infection. Recent studies highlighted that basophils can promote Th2 cytokine-mediated inflammation and that phenotypic and functional heterogeneity exists between classical IL-3-elicited basophils and thymic stromal lymphopoietin (TSLP)-elicited basophils. However, whether distinct basophil populations develop after helminth infection and their relative contributions to anti-helminth immune responses remain to be defined. After Trichinella spiralis infection of mice, we show that basophil responses are rapidly induced in multiple tissue compartments, including intestinal-draining lymph nodes. Trichinella-induced basophil responses were IL-3-IL-3R independent but critically dependent on TSLP-TSLPR interactions. Selective depletion of basophils after Trichinella infection impaired infection-induced CD4+ Th2 cytokine responses, suggesting that TSLP-dependent basophils augment Th2 cytokine responses after helminth infection. The identification and functional classification of TSLP-dependent basophils in a helminth infection model, coupled with their recently described role in promoting atopic dermatitis, suggests that these cells may be a critical population in promoting Th2 cytokine-associated inflammation in a variety of inflammatory or infectious settings. Collectively, these data suggest that the TSLP-basophil pathway may represent a new target in the design of therapeutic intervention strategies to promote or limit Th2 cytokine-dependent immunity and inflammation. Copyright © 2012 by The American Association of Immunologists, Inc.
    Original languageEnglish
    Pages (from-to)4371-4378
    Number of pages7
    JournalJournal of Immunology
    Volume189
    Issue number9
    DOIs
    Publication statusPublished - 1 Nov 2012

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