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

Hua Tang (1) , Weiping Cao (1) , Sudhir Pai Kasturi (1) , Rajesh Ravindran (1) , Helder I Nakaya (1) , Kousik Kundu (2) , Niren Murthy (2) , Thomas B Kepler (3) , Bernard Malissen (4) , Bali Pulendran (1)

1 Emory Vaccine Center
2 Georgia Institute of Technology [Atlanta]
3 Duke University [Durham]
4 CIML - Centre d'Immunologie de Marseille - Luminy

The mechanisms that initiate T helper type 2 (T(H)2) responses are poorly understood. Here we demonstrate that cysteine protease-induced T(H)2 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 T(H)2 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 T(H)1-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 T(H)2 response to cysteine proteases requires DC-basophil cooperation via ROS-mediated signaling.

Domaines: Immunologie

Hua Tang, Weiping Cao, Sudhir Pai Kasturi, Rajesh Ravindran, Helder I Nakaya, et al.. The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling.. Nature Immunology, 2010, 11 (7), pp.608-17. ⟨10.1038/ni.1883⟩. ⟨hal-00553489⟩