ILC2s activated by IL-25 promote antigen-specific Th2 and Th9 functions that contribute to the control of Trichinella spiralis infection.
IL-25, an IL-17 family cytokine, derived from epithelial cells was shown to regulate Th2- and Th9-type immune responses. We previously reported that IL-25 was important in promoting efficient protective immunity against T. spiralis infection; however, the cellular targets of IL-25 to elicit type-2 immunity during infection have not yet been addressed. Here, we investigated IL-25-responding cells and their involvement in mediating type-2 immune response during T. spiralis infection. ILC2 and CD4+ Th2 cells residing in the gastrointestinal tract of T. spiralis infected mice were found to express high levels of surface interleukin-17 receptor B (IL-17RB), a component of the IL-25 receptor. Following T. spiralis infection, activated ILC2s upregulated surface MHCII expression and enhanced capacity of effector T helper cell in producing antigen-specific Th2 and Th9 cytokines through MHCII-dependent interactions. Reciprocally, lack of CD4+ T helper cells impaired ILC2 function to produce type 2-associated cytokines in responding to IL-25 during T. spiralis infection. Furthermore, mice deficient in IL-17RB showed markedly reduced ILC2 numbers and antigen-specific Th2 and Th9 cytokine production during T. spiralis infection. The Il17rb-/- mice failed to mount effective antigen specific Th2 and Th9 functions resulting in diminished goblet cell and mast cell responses, leading to delayed worm expulsion in the intestines and muscles. Thus, our data indicated that ILC2s and CD4+ Th2 cells are the predominant cellular targets of IL-25 following T. spiralis infection and their collaborative interactions may play a key role in mounting effective antigen-specific Th2 and Th9 cytokine responses against T. spiralis infection.
- 1Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani Thailand.
- 2Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani Thailand.
- 3Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani Thailand.
- 4Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani Thailand.
- 5Center of Excellence for Flow Cytometry, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
- 6Division of Allergy and Immunology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH United States of America.
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||Last Modified: 2016-03-27