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*
Schistosomiasis Immunology and Pathology Unit, Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Preclinical Research, Genetics Institute, Andover, MA 01810;
Genetics Institute, Cambridge, MA 02140; and
§
The Biomedical Research Institute, Rockville, MD 20852
Schistosoma mansoni egg-induced pulmonary granuloma
formation is a cell-mediated inflammatory response associated with
dominant Th2-type cytokine expression, tissue eosinophilia, and high
levels of serum IgE. In the present study, we show that in vivo
blockade of the Th2 cytokine IL-13, using soluble IL-13R 
2-Fc fusion
protein, significantly reduced the size of pulmonary granulomas in
unsensitized as well as egg-sensitized mice. Blocking IL-13 also
significantly reduced total serum IgE levels. Interestingly, however,
IL-13 blockade did not affect the evolving egg-induced Th2-type
cytokine response. IL-4, IL-5, as well as IL-13 responses were
indistinguishable in control-Fc- and soluble IL-13R 2-Fc fusion
protein-treated animals. The smaller granulomas were also
phenotypically like the control Fc-treated mice, displaying a similar
eosinophil content. Additional studies in IL-4-deficient mice
demonstrated that IL-13 was produced, but at much lower levels than in
wild-type mice, while IL-4 expression was completely independent of
IL-13. Moreover, while granuloma formation was partially reduced in
IL-4-deficient mice, blocking IL-13 in these animals almost completely
abrogated granuloma development and the pulmonary eosinophilia, while
it simultaneously increased IFN-
production. Together, these data
demonstrate that IL-13 serves as an important mediator of Th2-mediated
inflammation and plays a role in eliciting IgE responses triggered by
schistosome eggs.
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M. Hesse, M. Modolell, A. C. La Flamme, M. Schito, J. M. Fuentes, A. W. Cheever, E. J. Pearce, and T. A. Wynn Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1/Type 2 Cytokines In Vivo: Granulomatous Pathology Is Shaped by the Pattern of L-Arginine Metabolism J. Immunol., December 1, 2001; 167(11): 6533 - 6544. [Abstract] [Full Text] [PDF]
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L. I. Terrazas, K. L. Walsh, D. Piskorska, E. McGuire, and D. A. Harn Jr. The Schistosome Oligosaccharide Lacto-N-neotetraose Expands Gr1+ Cells That Secrete Anti-inflammatory Cytokines and Inhibit Proliferation of Naive CD4+ Cells: A Potential Mechanism for Immune Polarization in Helminth Infections J. Immunol., November 1, 2001; 167(9): 5294 - 5303. [Abstract] [Full Text] [PDF]
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C. G. Lee, R. J. Homer, Z. Zhu, S. Lanone, X. Wang, V. Koteliansky, J. M. Shipley, P. Gotwals, P. Noble, Q. Chen, et al. Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor {beta}1 J. Exp. Med., September 17, 2001; 194(6): 809 - 822. [Abstract] [Full Text] [PDF]
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A. C. La Flamme, E. A. Patton, B. Bauman, and E. J. Pearce IL-4 Plays a Crucial Role in Regulating Oxidative Damage in the Liver During Schistosomiasis J. Immunol., February 1, 2001; 166(3): 1903 - 1911. [Abstract] [Full Text] [PDF]
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 R. Umeshita-Suyama, R. Sugimoto, M. Akaiwa, K. Arima, B. Yu, M. Wada, M. Kuwano, K. Nakajima, N. Hamasaki, and K. Izuhara Characterization of IL-4 and IL-13 signals dependent on the human IL-13 receptor {alpha} chain 1: redundancy of requirement of tyrosine residue for STAT3 activation Int. Immunol., November 1, 2000; 12(11): 1499 - 1509. [Abstract] [Full Text] [PDF]
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M. R. Potter, N. Noben-Trauth, J. H. Weis, C. Teuscher, and J. J. Weis Interleukin-4 (IL-4) and IL-13 Signaling Pathways Do Not Regulate Borrelia burgdorferi-Induced Arthritis in Mice: IgG1 Is Not Required for Host Control of Tissue Spirochetes Infect. Immun., October 1, 2000; 68(10): 5603 - 5609. [Abstract] [Full Text] [PDF]
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M. Hesse, A. W. Cheever, D. Jankovic, and T. A. Wynn NOS-2 Mediates the Protective Anti-Inflammatory and Antifibrotic Effects of the Th1-Inducing Adjuvant, IL-12, in a Th2 Model of Granulomatous Disease Am. J. Pathol., September 1, 2000; 157(3): 945 - 955. [Abstract] [Full Text] [PDF]
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M. Throsby, A. Herbelin, J.-M. Pleau, and M. Dardenne CD11c+ Eosinophils in the Murine Thymus: Developmental Regulation and Recruitment upon MHC Class I-Restricted Thymocyte Deletion J. Immunol., August 15, 2000; 165(4): 1965 - 1975. [Abstract] [Full Text] [PDF]
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J. Urban, H. Fang, Q. Liu, M. J. Ekkens, S.-J. Chen, D. Nguyen, V. Mitro, D. D. Donaldson, C. Byrd, R. Peach, et al. IL-13-Mediated Worm Expulsion Is B7 Independent and IFN-{gamma} Sensitive J. Immunol., April 15, 2000; 164(8): 4250 - 4256. [Abstract] [Full Text] [PDF]
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P. G. Fallon, E. J. Richardson, G. J. McKenzie, and A. N. J. McKenzie Schistosome Infection of Transgenic Mice Defines Distinct and Contrasting Pathogenic Roles for IL-4 and IL-13: IL-13 Is a Profibrotic Agent J. Immunol., March 1, 2000; 164(5): 2585 - 2591. [Abstract] [Full Text] [PDF]
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B. Johansson, S. Ingvarsson, P. Bjorck, and C. A. K. Borrebaeck Human Interdigitating Dendritic Cells Induce Isotype Switching and IL-13-Dependent IgM Production in CD40-Activated Naive B Cells J. Immunol., February 15, 2000; 164(4): 1847 - 1854. [Abstract] [Full Text] [PDF]
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D. L. Martin, C. L. King, E. Pearlman, E. Strine, and F. P. Heinzel IFN-{gamma} Is Necessary But Not Sufficient for Anti-CD40 Antibody-Mediated Inhibition of the Th2 Response to Schistosoma mansoni Eggs J. Immunol., January 15, 2000; 164(2): 779 - 785. [Abstract] [Full Text] [PDF]
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M. G. Chiaramonte, M. Hesse, A. W. Cheever, and T. A. Wynn CpG Oligonucleotides Can Prophylactically Immunize Against Th2-Mediated Schistosome Egg-Induced Pathology by an IL-12-Independent Mechanism J. Immunol., January 15, 2000; 164(2): 973 - 985. [Abstract] [Full Text] [PDF]
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N. Hayashi, K. Matsui, H. Tsutsui, Y. Osada, R. T. Mohamed, H. Nakano, S.-i. Kashiwamura, Y. Hyodo, K. Takeda, S. Akira, et al. Kupffer Cells from Schistosoma mansoni-Infected Mice Participate in the Prompt Type 2 Differentiation of Hepatic T Cells in Response to Worm Antigens J. Immunol., December 15, 1999; 163(12): 6702 - 6711. [Abstract] [Full Text] [PDF]
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F. P. Heinzel and R. A. Maier Jr. Interleukin-4-Independent Acceleration of Cutaneous Leishmaniasis in Susceptible BALB/c Mice following Treatment with Anti-CTLA4 Antibody Infect. Immun., December 1, 1999; 67(12): 6454 - 6460. [Abstract] [Full Text] [PDF]
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P. W. Mola, I. O. Farah, T. M. Kariuki, M. Nyindo, R. E. Blanton, and C. L. King Cytokine Control of the Granulomatous Response in Schistosoma mansoni-Infected Baboons: Role of Exposure and Treatment Infect. Immun., December 1, 1999; 67(12): 6565 - 6571. [Abstract] [Full Text] [PDF]
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D. Artis, N. E. Humphreys, A. J. Bancroft, N. J. Rothwell, C. S. Potten, and R. K. Grencis Tumor Necrosis Factor {alpha} Is a Critical Component of Interleukin 13–mediated Protective T Helper Cell Type 2 Responses during Helminth Infection J. Exp. Med., October 4, 1999; 190(7): 953 - 962. [Abstract] [Full Text] [PDF]
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D. Jankovic, M. C. Kullberg, N. Noben-Trauth, P. Caspar, J. M. Ward, A. W. Cheever, W. E. Paul, and A. Sher Schistosome-Infected IL-4 Receptor Knockout (KO) Mice, in Contrast to IL-4 KO Mice, Fail to Develop Granulomatous Pathology While Maintaining the Same Lymphokine Expression Profile J. Immunol., July 1, 1999; 163(1): 337 - 342. [Abstract] [Full Text] [PDF]
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N. Noben-Trauth, W. E. Paul, and D. L. Sacks IL-4- and IL-4 Receptor-Deficient BALB/c Mice Reveal Differences in Susceptibility to Leishmania major Parasite Substrains J. Immunol., May 15, 1999; 162(10): 6132 - 6140. [Abstract] [Full Text] [PDF]
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A. W. Cheever, R. W. Poindexter, and T. A. Wynn Egg Laying Is Delayed but Worm Fecundity Is Normal in SCID Mice Infected with Schistosoma japonicum and S. mansoni with or without Recombinant Tumor Necrosis Factor Alpha Treatment Infect. Immun., May 1, 1999; 67(5): 2201 - 2208. [Abstract] [Full Text] [PDF]
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 I.-C. HO, J.I. KIM, S.J. SZABO, and L.H. GLIMCHER Tissue-specific Regulation of Cytokine Gene Expression Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 573 - 584. [Abstract] [PDF]
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