13:40 - 15:10
Room: ANA Crowne Plaza “Ohtori” Room C
Workshop Session
Chair/s:
Cem Gabay, Hiroki Yoshida
IL-33 potentiates the inflammatory response to Toxoplasma gondii
Joseph Thomas Clark, Jeongho Park, Christoph Konradt, Maxime Jacquet, Christopher Hunter
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United States

Mice deficient in the IL-33 receptor ST2 are susceptible to infection with the protozoan parasite Toxoplasma gondii, but how IL-33 promotes resistance to infection remains elusive. Previous reports have attributed this susceptibility to aberrant skewing of the immune response away from type 2 immunity, with which ST2 has been classically associated, toward an excessive type 1 response and consequent lethal immune pathology in the central nervous system (CNS). Although expression of ST2 by tissue-resident Tregs supports a possible deficiency in immune regulation, ST2-knockout mice were also found to have higher parasite burdens in the CNS, suggesting a potential defect in the inflammatory response. In recent years, a direct role for IL-33/ST2 in enhancing type 1 responses has been appreciated, leading us to reconsider the function of IL-33 in the response to T. gondii. Using whole organ in vitro antigen recall assays of spleen, bone marrow, and brain tissues, we found that addition of exogenous IL-33 to Soluble Toxoplasma Antigen (STAg)-restimulated cultures enhanced interferon gamma production during both acute and chronic infection. Further, we observed that IL-33 enhanced the proliferation and differentiation of restimulated parasite-specific CD4+ and CD8+ effector T cells in vitro. To confirm the physiological relevance of our system, we used IL-33 reporter mice to confirm in vivo expression of IL-33 in intact tissues relevant to T. gondii infection, including the meninges and cervical lymph nodes. As IL-33 is expressed at high levels in many tissues, including the central nervous system, and is released during tissue damage caused by infections such as T. gondii, these results suggest that IL-33 enhances the inflammatory response to T. gondii and consequently control of this parasitic infection.


Reference:
Tu-WS11-6
Session:
Workshop 11, “Emerging cytokines”
Presenter/s:
Joseph Thomas Clark
Presentation type:
Oral Presentation
Room:
ANA Crowne Plaza “Ohtori” Room C
Chair/s:
Cem Gabay, Hiroki Yoshida
Date:
Tuesday, 31 October 2017
Time:
14:58 - 15:08
Session times:
13:40 - 15:10