title: Thymic stromal lymphopoietin-dependent basophils promote Th2 cytokine responses following intestinal helminth infection.
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.
authors.affiliation: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Giacomin
authors.forename: Mark C
authors.initials: MC
authors.lastname: Siracusa
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Walsh
authors.forename: Richard K
authors.initials: RK
authors.lastname: Grencis
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.forename: David
authors.initials: D
authors.lastname: Artis
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017154:Stromal Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin