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* Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and
Division of Immunology, Children’s Hospital, Harvard Medical School, Boston, MA 02115; and
Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, United Kingdom
Although the innate immune function of mast cells in the acute phase of parasitic and bacterial infections is well established, their participation in chronic immune responses to indolent infection remains incompletely understood. In parasitic infection with Trichinella spiralis, the immune response incorporates both lymphocyte and mast cell-dependent effector functions for pathogen eradication. Among the mechanistic insights still unresolved in the reaction to T. spiralis are the means by which mast cells respond to parasites and the mast cell effector functions that contribute to the immunologic response to this pathogen. We hypothesized that mast cell elaboration of tryptase may comprise an important effector component in this response. Indeed, we find that mice deficient in the tryptase mouse mast cell protease-6 (mMCP-6) display a significant difference in their response to T. spiralis larvae in chronically infected skeletal muscle tissue. Mechanistically, this is associated with a profound inability to recruit eosinophils to larvae in mMCP-6-deficient mice. Analysis of IgE-deficient mice demonstrates an identical defect in eosinophil recruitment. These findings establish that mast cell secretion of the tryptase mMCP-6, a function directed by the activity of the adaptive immune system, contributes to eosinophil recruitment to the site of larval infection, thereby comprising an integral link in the chronic immune response to parasitic infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by National Institutes of Health Grants AI059746-01, HL036110, AI031599, and AI05447, an Arthritis Foundation postdoctoral fellowship (100972), and the Cogan Family Foundation. A.D.P. was funded by the Veterinary Training Research Initiative (VT0102).
2 Address correspondence and reprint requests to Dr. David M. Lee, 1 Jimmy Fund Way, Smith Building Room 552B, Boston, MA 02115. E-mail address: dlee{at}rics.bwh.harvard.edu
3 Abbreviations used in this paper: MMC, mucosal mast cell; CTMC, connective tissue-type mast cell; mMCP, mouse mast cell protease; LPF, low power field.
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