Immunology Graduate Group

Christopher A. Hunter, Ph.D. Professor and Chair, Department of Pathobiology School of Veterinary Medicine 310F Hill Pavilion 380 S. University Avenue Philadelphia, PA 19104 Office Phone:  (215) 573-7772 Lab Phone: (215) 573-5139 Fax: (215) 746-2295 Email:  chunter@phl.vet.upenn.edu Education: Ph.D., University of Glasgow B.Sc., University of Glasgow Research Interests Host-pathogen interactions, cytokines, innate and adaptive immunity to infection Research Summary The Hunter laboratory has several areas of research that center around understanding how the immune system deals with T. gondii. The first focuses on host pathogen interactions at the cellular level and how the parasite interacts with intracellular signaling pathways (NF-kB/JAK-STAT). In collaboration with the Roos laboratory, genetic approaches are being used to identify parasite factors that are involved in these events. This is part of work in progress which has used transgenic parasites to address fundamental questions about which cells are important in the initiation of adaptive immunity and the role of cross-presentation in the development of T cell responses. These latter studies compliment the work in the laboratory that has helped to define the cytokine networks that regulate the balance between protective and pathological immune responses and current studies focus on the IL-6 family of cytokines in these events. Lastly the laboratory is interested in better understanding the pathogenesis of toxoplasmic encephalitis (TE) in the immunocompromised patients who develop this disease. This work has also led the laboratory to try and apply what we have learned in TE to better understand the neuro-pathogenesis of African sleeping sickness. The production of IFN-g by NK cells is important for re- sistance to Toxoplasma. While the ability of IL-12 to stim- ulate NK cells is central to this mechanism of resistance, the effects of IL-12 are enhanced by many additional co-factors such as the Type I interferons, IL-2, CD28, IL-1, IGIF and TNF-a. 0This figure represents the receptors that are involved in the regulation of NK cell production of IFN-g.

Selected Publications

Villarino, Alejandro V. Tato, Cristina M. Stumhofer, Jason S. Yao, Zhengju. Cui, Yongzhi K. Hennighausen, Lothar. O'Shea, John J. Hunter, Christopher A.: Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals. Journal of Experimental Medicine 204(1): 65-71, Jan 22 2007.

Dzierszinski, F., Pepper, M., La Rosa, D., Wilson, E., Bzik, D., Turka, L., Hunter, CA. and Roos, D.: Antigen presentation through MHC class I occurs via the endogenous pathway in non-hematopoietic cells and professional phagocytes infected with Toxoplasma gondii Infection Immunity 75: 5200-9, 2007.

Stumhofer, J.S., J.S. Silver, A. Laurence, P.M. Porrett, T.H. Harris, L.A. Turka, M. Ernst, C.J. Saris, J.J. O'Shea, and C.A. Hunter.: Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol Page: 1363-1371, 11 2007.

Kastelein, Robert A. Hunter, Christopher A. Cua, Daniel J.: Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. [Review] [86 refs] Annual Review of Immunology 25: 221-42, 2007.

Masek, Katherine S. Fiore, Jim. Leitges, Michael. Yan, Shi-Fang. Freedman, Bruce D. Hunter, Christopher A.: Host cell Ca2+ and protein kinase C regulate innate recognition of Toxoplasma gondii. Journal of Cell Science 119(Pt 21): 4565-73, Nov 1 2006.

Stumhofer, Jason S. Laurence, Arian. Wilson, Emma H. Huang, Elaine. Tato, Cristina M. Johnson, Leanne M. Villarino, Alejandro V. Huang, Qiulong. Yoshimura, Akihiko. Sehy, David. Saris, Christiaan J M. O'Shea, John J. Hennighausen, Lothar. Ernst, Matthias. Hunter, Christopher A.: Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system.[see comment]. Nature Immunology 7(9): 937-45, Sep 2006.

Wilson, Emma H. Zaph, Colby. Mohrs, Markus. Welcher, Andy. Siu, Jerry. Artis, David. Hunter, Christopher A.: B7RP-1-ICOS interactions are required for optimal infection-induced expansion of CD4+ Th1 and Th2 responses. Journal of Immunology 177(4): 2365-72, Aug 15 2006.

Villarino, Alejandro V. Stumhofer, Jason S. Saris, Christiaan J M. Kastelein, Robert A. de Sauvage, Frederic J. Hunter, Christopher A.: IL-27 limits IL-2 production during Th1 differentiation. Journal of Immunology 176(1): 237-47, Jan 1 2006.

Shapira, Sagi. Harb, Omar S. Margarit, Juan. Matrajt, Mariana. Han, Jerry. Hoffmann, Alexander. Freedman, Bruce. May, Michael J. Roos, David S. Hunter, Christopher A.: Initiation and termination of NF-kappaB signaling by the intracellular protozoan parasite Toxoplasma gondii. Journal of Cell Science 118(Pt 15): 3501-8, Aug 1 2005.

Pepper, Marion. Dzierszinski, Florence. Crawford, Amy. Hunter, Christopher A. Roos, David.: Development of a system to study CD4+-T-cell responses to transgenic ovalbumin-expressing Toxoplasma gondii during toxoplasmosis. Infection & Immunity 72(12): 7240-6, Dec 2004.

Villarino, Alejandro. Hibbert, Linda. Lieberman, Linda. Wilson, Emma. Mak, Tak. Yoshida, Hiroki. Kastelein, Robert A. Saris, Christiaan. Hunter, Christopher A.: The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection.[see comment]. Immunity 19(5): 645-55, Nov 2003.

Tato, C.M., G. Martins, F.A. High, K. DiCoco, S.L. Reiner and C.A. Hunter: Cutting Edge: Early production of IFN-? by NK cells is independent of epigenetic modification of the IFN-? promoter. Journal Immunology Page: 1514-1518, 2003.

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