The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling.
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.
Tang
Hua
H
Emory Vaccine Center, Atlanta, Georgia, USA.
Cao
Weiping
W
Kasturi
Sudhir Pai
SP
Ravindran
Rajesh
R
Nakaya
Helder I
HI
Kundu
Kousik
K
Murthy
Niren
N
Kepler
Thomas B
TB
Malissen
Bernard
B
Pulendran
Bali
B
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000276:immunology; D001491:Basophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015847:Interleukin-4 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010206:Papain / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D033942:Adaptor Proteins, Vesicular Transport; D000941:Antigens; D016207:Cytokines; D015847:Interleukin-4; D010206:Papain; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4; D000094632:Thymic Stromal Lymphopoietin; C476286:Ticam1 protein, mouse; C000721967:TSLP protein, mouse