STUDY SUPPORTS CHRONIC LYME

From: PrincessKiara70 (princesskiara70_at_aol.com)
Date: 12/04/04 

Date: 04 Dec 2004 20:46:29 GMT

3 December 2004

STUDY SUPPORTS CHRONIC LYME

Protective Niche for Borrelia burgdorferi to Evade Humoral Immunity

Fang Ting Liang*, Eric L. Brown, Tian Wang*, Renato V. Iozzo and Erol
Fikrig*

>From the Department of Internal Medicine,* Section of Rheumatology,
Yale University School of Medicine, New Haven, Connecticut; the
Center for Extracellular Matrix Biology, Texas A&M University System
Health Science Center, Albert B. Alkek Institute of Biosciences and
Technology, Houston, Texas; and the Department of Pathology, Anatomy,
and Cell Biology, Thomas Jefferson University, Philadelphia,
Pennsylvania

The Lyme disease spirochete, Borrelia burgdorferi, is an extracellular
microbe that causes persistent infection despite the development of
strong immune responses against the bacterium. B. burgdorferi
expresses several ligand-binding lipoproteins, including the decorin-
binding proteins (Dbps) A and B, which may mediate attachment to
decorin, a major component of the host extracellular matrix during
murine infection. We show that B. burgdorferi was better protected in
the joints and skin, two tissues with a higher decorin expression,
than in the urinary bladder and heart, two tissues with a lower
decorin expression, during chronic infection of wild-type mice.

Targeted disruption of decorin alone completely abolished
the protective niche in chronically infected decorin-deficient mice
but did not affect the spirochete burden during early infection. The
nature of protection appeared to be specific because the spirochetes
with higher outer surface protein C expression were not protected
while the protective niche seemed to favor the spirochetes with a
higher dbpA expression during chronic infection.

These data suggest that spirochetal DbpA may interact with host
decorin during infection and such interactions could be a mechanism
that B. burgdorferi uses to evade humoral immunity and establish
chronic infection.

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Yale University; Borrelia burgdorferi changes antigens based on host
immune response 08 December 2004 Biotech Week Copyright 2004, Biotech
Week via NewsRx.com (NewsRx.com & NewsRx.net)

-- Borrelia burgdorferi changes its surface antigenic expression in
response to host immune responses. The Lyme disease spirochete,
Borrelia burgdorferi, causes persistent mammalian infection despite
the development of vigorous immune responses against the pathogen. To
examine spirochetal phenotypes that dominate in the hostile immune
environment, the mRNA transcripts of four prototypic surface
lipoproteins, decorin-binding protein A (DbpA), outer surface protein
C (OspC), BBF01, and VlsE, were analyzed by quantitative reverse
transcription-PCR under various immune conditions. We demonstrate
that B. burgdorferi changes its surface antigenic expression in
response to immune attack," investigators in the United States
report. TD "dbpA expression was unchanged while the spirochetes
decreased ospC expression by 446 times and increased BBF01 and vlsE
expression up to 20 and 32 times, respectively, under the influence
of immune pressure generated in immunocompetent mice during
infection," stated Fang Ting Liang and collaborators at Yale
University, Centocor, Inc., and the Centers for Disease Control and
Prevention. "This change in antigenic expression could be induced by
passively immunizing infected severe combined immunodeficiency mice
with specific Borrelia antisera or OspC antibody and appears to allow
B. burgdorferi to resist immune attack." Liang and associates
published their study in Infection and Immunity (Borrelia burgdorferi
changes its surface antigenic expression in response to host immune
responses.

Infec Immunity, 2004;72(10):5759-5767). For additional information,
contact Erol Fikrig, Section of Rheumatology, Department of Internal
Medicine, Yale University School of Medicine, S525A, 300 Cedar
Street, New Haven, CT 06520-8031, USA.

E-mail: erol.fikrig@y.... The publisher of the journal Infection and
Immunity can be contacted at: American Society for Microbiology, 1752
N Street NW, Washington, DC 20036-2904, USA. The information in this
article comes under the major subject areas of Lyme Disease, Tick-
Borne Disease, Zoonosis, Lyme Disease Vaccine, Vaccine Development,
Proteomics, Immunotherapy, and Immunology. This article was prepared
by Biotech Week editors from staff and other reports. Copyright 2004,
Biotech Week via NewsRx.com & NewsRx.net.

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http://yalemedicalgroup.org/news/ymg_fikrig.html

Lyme Disease Receptor Identified in Tick Guts

[November 2004] Researchers at Yale School of Medicine have
identified a Lyme disease receptor called TROSPA that is used by
disease agents to invade ticks.

Lyme disease, the most common tick-borne disease in the United
States, is caused by spirochete bacteria Borrelia burgdorferi, which
also cause arthritis in humans. The purpose of the study, published
November 12 in the journal Cell, was to identify how Lyme disease
pathogens survive inside ticks.

"We identified a receptor inside the tick gut that the spirochete
bacteria use to colonize or invade ticks," said principal
investigator Erol Fikrig, M.D., professor of internal
medicine/rheumatology and in the Section of Microbial Pathogenesis,
and Department of Epidemiology and Public Health at Yale School of
Medicine.

"When we eliminated or blocked the receptor in the ticks, they were
no longer able to carry the Lyme disease agent Borellia
burgforferi."

"This opens up potential new avenues to disrupt the Borellia's life
cycle and offers strategies for improving diagnosis and treatment of
Lyme disease," Fikrig added.

To characterize the Lyme disease receptor, the team cloned the gene
for the receptor from ticks. After they expressed the purified
receptor gene, they showed that the Lyme disease agent Borellia
burgforferi binds to the receptor. "When we blocked the receptors
with antibodies or when we used RNA interference to knock the
receptor out of the ticks, they no longer carried Borellia
burgforferi," said Fikrig.

"We are excited to learn more about the life cycle of this important
pathogen," Fikrig added. "This information can also be used to study
other vector-borne diseases such as West Nile virus and Malaria,"
Fikrig added.

Other authors on the study included Utpal Pal, Xin Li, Tian Wang,
Ruth R. Montgomery, Nandhini Ramamoorthi, Aravinda M. deSilva, Fukai
Bao, Xiaofeng Yang, Marc Pypaert, Deepti Pradhan, Fred S. Kantor, Sam
Telford and John F. Anderson.

Citation: Cell, No. 19 Volume 4, November 12, 2004

More about Erol Fikrig, MD

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