Penn Veterinary Medicine | University of Pennsylvania

Description of Research Expertise

Description of Research
The goals of the lab are to gain a better understanding of the immuno-regulatory mechanisms that govern the initiation, regulation, and development of immune effector responses following infection with pathogens of the gastrointestinal tract. The gut is a unique immunologic niche, simultaneously maintaining tolerance to food antigens and billions of enteric bacterial symbionts, while retaining the ability to recognize and respond to potentially dangerous pathogens.

We are particularly interested in gut-dwelling helminth parasites. An estimated two billion people world-wide are infected with soil transmitted helminth parasites, with 300 million people suffering severe infections. In addition, this group of pathogens represents a significant economic burden to the livestock industry. Despite their ubiquitous distribution and evolutionary success, many of the pathogen factors that promote parasitism and the host factors that mediate resistance to these infections remain poorly defined.

Trichuris muris is one of the model systems we use to investigate the cellular and molecular mechanisms that govern immunity and inflammation following infection. T. muris is a natural gastrointestinal parasite of mice and provides an immunologically well-defined model of human and veterinary infections. Previous studies have shown that CD4+ T helper type 1 (Th1) responses promote chronic infection, while CD4+ Th2 responses are required for host protective immunity. However, the cellular and molecular mechanisms that control how Trichuris is recognized by the innate immune system, how CD4+ T helper cell differentiation is regulated in the gut, and what the immune effector mechanisms are that mediate expulsion of these infections are unknown.

Selected Publications

Nair, MG, Du, Y, Perrigoue, JG, Zaph, C, Taylor, JJ, Goldschmidt, M, Yancopoulos, GD, Valenzuela, DM, Murphy, A, Karow, M, Stevens, S, Pearce EJ, Artis. D.: Alternatively activated macrophage-derived RELMa is a negative regulator of type 2 inflammation in the lung. Journal of Experimental Medicine 206: 937-952, 2009.

Perrigoue JG, Saenz SA, Siracusa M, Allenspach EJ, Taylor BC, Giacomin PR, Nair MG, Du Y, Zaph C, van Rooijen N, Comeau MR, Pearce EJ, Laufer TM, and Artis D.: MHC class II-dependent basophil-CD4+ T cell interactions promote Th2 cytokine-dependent immunity. Nature Immunology 10: 697-705, 2009.

Taylor BC, Zaph C, Troy AE, Du Y, Guild KJ, Comeau MR, Artis D. : TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. Journal of Experimental Medicine 206: 655-667, 2009.

Hoffmann, C., Hill, D. A., Minkah, N., Kirn, T., Troy, A., Artis, D., Bushman, F.: Community-wide response of gut microbiota to enteropathogenic Citrobacter infection revealed by deep sequencing. Infection and Immunity Page: In press, 2009.

Perrigoue JG, Zaph C, Guild K, Du Y, and Artis D.: IL-31-IL-31R interactions limit the magnitude of Th2 cytokine-dependent immunity following intestinal helminth infection. Journal of Immunology 182(PMID:19414760]): 6088-94, 2009.

Troy, A. E., Zaph, C., Du, Y., Taylor, B. C., Guild, K. J., Hunter, C. A., Saris, C. J., Artis, D.: IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis. Journal of Immunology 183([PMID: 19596985]): 2037-44, 2009.

Villarino, A. V., Artis, D., Bezbradica, J. S., Miller, O., Saris, C. J., Joyce, S., Hunter, C. A.: IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int Immunol 20([PMID: 18375937]): 739-752, 2008.

Perona-Wright, G, Mohrs, K, Taylor, J, Zaph, C, Artis, D, Pearce, EJ, Mohrs, M: Cutting edge: Helminth infection induces IgE in the absence of mu- or delta-chain expression. Journal of Immunology 181([PMID: 18981085]): 6697-6701, 2008.

Nair, M, Guild, K, Du, Y, Zaph, C, Yancopoulos, GD, Valenzuela, DM, Murphy, A, Stevens, S, Karow, M, Artis, D.: Goblet Cell-Derived Resistin-Like Molecule beta Augments CD4+ T Cell Production of IFN-{gamma} and Infection-Induced Intestinal Inflammation. Journal of Immunology 181([PMID: 18802073]): 4709 - 4715, 2008.

Zaph, C, Du, Y, Saenz, SA, Nair, MG, Perrigoue, JG, Taylor, BC, Troy, AE, Kobuley, DE, Kastelein, RA, Cua, D, Yu, Y, Artis. D.: Commensal-dependent expression of IL-25 regulates the IL-23–IL-17 axis in the intestine J. Exp. Med 2008.