Anaplasma phagocytophilum-Borrelia burgdorferi Coinfection Enhances Chemokine, Cytokine, and Matrix Metalloprotease Expression by Human Brain Microvascular Endothelial Cells

http://cvi.asm.org/cgi/content/short/14/11/1420

Clinical and Vaccine Immunology, November 2007, p. 1420-1424, Vol. 14,
No. 11
doi:10.1128/CVI.00308-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Dennis J. Grab,1*
Elvis Nyarko,1#
Nicole C. Barat,2
Olga V. Nikolskaia,1
and J. Stephen Dumler,2

(1) Department of Pediatrics, Johns Hopkins University School of
Medicine, Baltimore, Maryland 21287
(2) Department of Pathology, Johns Hopkins University School of
Medicine, Baltimore, Maryland 21205

Received 26 July 2007/ Returned for modification 12 September 2007/
Accepted 19 September 2007
Published ahead of print on 26 September 2007.

Borrelia burgdorferi and Anaplasma phagocytophilum coinfect and are
transmitted by Ixodes species ticks. Clinical indicators suggest that A.
phagocytophilum coinfection contributes to the 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 (MMP-1, -3, -7,
-8, and -9), cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis
factor alpha), and chemokines (IL-8 and macrophage inflammatory protein
1{alpha}) known to affect vascular permeability and inflammatory responses.

* Corresponding author. Mailing address: Department of Pediatrics, Johns
Hopkins University School of Medicine, 200 North Wolfe Street, Room
3147, Baltimore, MD 21287. Phone: (410) 614-3917. Fax: (410) 614-1491.
E-mail: dgrab@jhmi.edu

# Present address: Department of Oceanography and Fisheries, University
of Ghana, Legon, Accra, Ghana.

Clinical and Vaccine Immunology, November 2007, p. 1420-1424, Vol. 14,
No. 11
doi:10.1128/CVI.00308-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved