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: Paul R Giacomin, Mark C Siracusa, Kevin P Walsh, Richard K Grencis, Masato Kubo, Michael R Comeau, David Artis
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 189 Issue 9 Pg. 4371-8 (Nov 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 23024277 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Thymic Stromal Lymphopoietin

Topics

• Animals
• Basophils (immunology, parasitology, pathology)
• Cytokines (biosynthesis, physiology)
• Inflammation (immunology, metabolism, parasitology)
• Intestinal Mucosa (immunology, parasitology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Stromal Cells (immunology, parasitology, pathology)
• Th2 Cells (immunology, parasitology, pathology)
• Thymus Gland (immunology, parasitology, pathology)
• Trichinella spiralis (immunology)
• Trichinellosis (immunology, metabolism, pathology)
• Thymic Stromal Lymphopoietin