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

• 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
• Journal Title: Nature Immunology
• Volume: Volume 11, Number 7
• Publisher: Nature Research (part of Springer Nature) | 2010-07, Pages 608-617
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/ni.1883
• Subjects: Health Sciences, Immunology; Engineering, Biomedical; Health Sciences, Pathology

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.