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*
U.S. Department of Agriculture, Beltsville, MD, 20705;
Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267 and Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220;
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
§
University of Manchester, Manchester, United Kingdom; and
¶
Genetics Institute, Cambridge, MA 02140
Studies in mice infected with the gastrointestinal nematode parasite Nippostrongylus brasiliensis demonstrated that IL-4/IL-13 activation of Stat6 suppresses development of intestinal mastocytosis and does not contribute to IL-4/IL-13 production, but is still essential for parasite expulsion. Because expulsion of another gastrointestinal nematode, Trichinella spiralis, unlike N. brasiliensis expulsion, is mast cell dependent, these observations suggested that T. spiralis expulsion would be Stat6 independent. Instead, we find that Stat6 activation by IL-4/IL-13 is required in T. spiralis-infected mice for the mast cell responses that induce worm expulsion and for the cytokine responses that induce intestinal mastocytosis. Furthermore, although IL-4 induces N. brasiliensis expulsion in the absence of B cells, T cells, and mast cells, mast cells and T cells are required for IL-4 induction of T. spiralis expulsion. Thus, Stat6 signaling is required for host protection against N. brasiliensis and T. spiralis but contributes to expulsion of these two worms by different mechanisms. The induction of multiple effector mechanisms by Stat6 signaling provides a way for a cytokine response induced by most gastrointestinal nematode parasites to protect against most of these parasites, even though different effector mechanisms are required for protection against different nematodes.
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W. I. Khan, B. A. Vallance, P. A. Blennerhassett, Y. Deng, E. F. Verdu, K. I. Matthaei, and S. M. Collins Critical Role for Signal Transducer and Activator of Transcription Factor 6 in Mediating Intestinal Muscle Hypercontractility and Worm Expulsion in Trichinella spiralis-Infected Mice Infect. Immun., February 1, 2001; 69(2): 838 - 844. [Abstract] [Full Text] [PDF]
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H. Schjerven, P. Brandtzaeg, and F.-E. Johansen Mechanism of IL-4-Mediated Up-Regulation of the Polymeric Ig Receptor: Role of STAT6 in Cell Type-Specific Delayed Transcriptional Response J. Immunol., October 1, 2000; 165(7): 3898 - 3906. [Abstract] [Full Text] [PDF]
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