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) All Versions of this Article: jimmunol.0901390v1 183/8/5279    most recent 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 Google Scholar Articles by Petzke, M. M. Articles by Schwartz, I. PubMed PubMed Citation Articles by Petzke, M. M. Articles by Schwartz, I.

Recognition of Borrelia burgdorferi, the Lyme Disease Spirochete, by TLR7 and TLR9 Induces a Type I IFN Response by Human Immune Cells¹

Mary M. Petzke,^2* Andrew Brooks, Michelle A. Krupna,^* Dana Mordue,^* and Ira Schwartz^*

^*Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595; and Bionomics Research and Technology Center, Robert Wood Johnson-University of Medicine and Dentistry of New Jersey/Rutgers University, Piscataway, NJ 08854

Borrelia burgdorferi is the spirochetal agent of Lyme disease, a multisystemic disorder characterized by inflammation. Using global transcriptional profiling, we characterized the response of human PBMCs exposed to B. burgdorferi in an ex vivo coculture system. The expression profiles induced by B. burgdorferi were marked by the intense up-regulation of IFN-responsive transcripts and transcripts involved in the JAK/STAT signaling pathway. Transcript levels of IFN-, IFN-β, and IRF7, and protein concentrations of IFN-, were significantly elevated relative to those in unstimulated PBMCs. The induction of IFN- was completely dependent upon phagocytosis of B. burgdorferi. Addition of a soluble type I IFN receptor, B18R, did not abolish the induction of IFN-inducible genes, indicating that B. burgdorferi directly elicits enhanced expression of these genes independently of type I IFN feedback signaling. Inhibitors of either TLR7 or TLR9 significantly reduced B. burgdorferi-stimulated IFN- protein expression and transcription of IFN-induced genes. Simultaneous inhibition of both TLR7 and TLR9 completely abrogated IFN- induction. The IFN--producing populations in PBMCs were identified as plasmacytoid dendritic and CD14⁺CD11c⁺ cells. These results reveal a TLR7/9-dependent signaling pathway used by human PBMCs to initiate a type I IFN response to the extracellular bacterium B. burgdorferi.

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 by Grant 5UO1CI000160 from the Centers for Disease Control and Prevention, Atlanta, GA.

² Address correspondence and reprint requests to Dr. Mary M. Petzke, Department of Microbiology and Immunology, New York Medical College, BSB Room 328, Valhalla, NY 10595. E-mail address: mary_petzke{at}nymc.edu

³ Abbreviations used in this paper: EM, erythema migrans; PAMP, pathogen-associated molecular pattern; MOI, multiplicity of infection; ODN, oligodeoxyribonucleotide; LAL, Limulus amebocyte lysis.