The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling

• Type of Material: Article
• Authors: Hua Tang, Emory University; Weiping Cao, Emory University; Sudhir Kasturi, Emory University; Rajesh Ravindran, Emory University; Helder Imoto Nakaya, Emory University; Kousik Kundu, Georgia Institute of Technology; Niren Murthy, Emory University; Thomas B Kepler, Duke University; Bernard Malissen, Université de la Méditerranée; Bali Pulendran, Emory University
• Language: English
• Date: 2010-07
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Nature America, Inc. All rights reserved.
• Final Published Version (URL): http://www.nature.com/ni/journal/v11/n7/full/ni.1883.html
• Title of Journal or Parent Work: Nature Immunology
• ISSN: 1529-2908
• Volume: 11
• Issue: 7
• Start Page: 608
• End Page: 617
• Grant/Funding Information: National Institutes of Health (U54AI057157, R37AI48638, R01DK057665, U19AI057266, HHSN266 200700006C, N01 AI50019, N01 AI50025); Bill & Melinda Gates Foundation
• Research Categories: Engineering, Biomedical; Health Sciences, Pathology; Health Sciences, Immunology

Abstract

The mechanisms that initiate T helper type 2 (TH2) responses are poorly understood. Here we demonstrate that cysteine protease–induced TH2 responses occur via ‘cooperation’ between migratory dermal dendritic cells (DCs) and basophils positive for interleukin 4 (IL-4). Subcutaneous immunization with papain plus antigen induced reactive oxygen species (ROS) in lymph node DCs and in dermal DCs and epithelial cells of the skin. ROS orchestrated TH2 responses by inducing oxidized lipids that triggered the induction of thymic stromal lymphopoietin (TSLP) by epithelial cells mediated by Toll-like receptor 4 (TLR4) and the adaptor protein TRIF; by suppressing production of the TH1-inducing molecules IL-12 and CD70 in lymph node DCs; and by inducing the DC-derived chemokine CCL7, which mediated recruitment of IL-4+ basophils to the lymph node. Thus, the TH2 response to cysteine proteases requires DC-basophil cooperation via ROS-mediated signaling.