CVI Accepts, published online ahead of print on 26 September 2007

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Clin. Vaccine Immunol. doi:10.1128/CVI.00308-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Chemokine, cytokine and matrix metalloprotease expression by human brain microvascular endothelial cells is enhanced with Anaplasma phagocytophilum-Borrelia burgdorferi coinfection

Dennis J Grab^*, Elvis Nyarko, Nicole C. Barat, Olga V. Nikolskaia, and J Stephen Dumler

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

^* To whom correspondence should be addressed. Email: dgrab{at}jhmi.edu.

Borrelia burgdorferi and Anaplasma phagocytophilum co-infect and are transmitted by Ixodes species ticks. Clinical indicators suggest that A. phagocytophilum coinfection contributes to severity, dissemination, and possibly sequelae of Lyme disease. Previous in vitro studies showed that spirochete penetration through human brain microvascular endothelial cells of the blood-brain barrier is facilitated by endothelial cell-derived matrix metalloproteases (MMPs). A. phagocytophilum-infected neutrophils continuously release MMPs and other vasoactive biomediators. We examined B. burgdorferi infection of brain microvascular barriers during A. phagocytophilum coinfection and showed that coinfection enhanced reductions in transendothelial electrical resistance and enhanced or synergistically increased production of MMPs (-1,-3,-7,-8,-9), cytokines (IL-6, IL-10, TNF), and chemokines (IL-8, MIP-1) known to affect vascular permeability and inflammatory responses.

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