HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Olson, C. M. Articles by Anguita, J. Search for Related Content PubMed PubMed Citation Articles by Olson, C. M., Jr. Articles by Anguita, J.

Local Production of IFN- by Invariant NKT Cells Modulates Acute Lyme Carditis¹

Chris M. Olson, Jr.^*, Tonya C. Bates^*, Hooman Izadi^*, Justin D. Radolf, Sally A. Huber, Jonathan E. Boyson and Juan Anguita^2,*

^* Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA 01003; Departments of Medicine and Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030; and Departments of Pathology and Laboratory Medicine and Surgery, University of Vermont College of Medicine, Burlington, VT 05401

The Lyme disease spirochete Borrelia burgdorferi is the only known human pathogen that directly activates invariant NKT (iNKT) cells. The number and activation kinetics of iNKT cells vary greatly among different strains of mice. We now report the role of the iNKT cell response in the pathogenesis of Lyme disease using C57BL/6 mice, a strain with optimal iNKT cell activation that is resistant to the development of spirochetal-induced inflammation. During experimental infection of B6 mice with B. burgdorferi, iNKT cells localize to the inflamed heart where they are activated by CD1d-expressing macrophages. Activation of iNKT cells in vivo results in the production of IFN-, which we demonstrate ameliorates the severity of murine Lyme carditis by at least two mechanisms. First, IFN- enhances the recognition of B. burgdorferi by macrophages, leading to increased phagocytosis of the spirochete. Second, IFN- activation of macrophages increases the surface expression of CD1d, thereby facilitating further iNKT activation. Collectively, our data demonstrate that in the resistant background, B6, iNKT cells modulate the severity of murine Lyme carditis through the action of IFN-, which appears to self-renew through a positive feedback loop during 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 work was supported in part by grants from the National Institutes of Health (AR048265 to J.A. and AI-29735 and AI38894 to J.D.R.) and a fellowship to C.M.O.J. from the American Heart Association.

² Address correspondence and reprint requests to Dr. Juan Anguita, Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, 103 Paige Laboratory, 161 Holdsworth Way, Amherst, MA 01003. E-mail address: janguita{at}vasci.umass.edu

³ Abbreviations used in this paper: iNKT, invariant NKT; BMM, bone marrow-derived macrophages; iTCR, invariant TCR; moi, multiplicity of infection; rmIFN-, recombinant murine IFN-.