Chlamydia May Play Role In a Type of Arthritis

Linda — Mon, 23 Nov 2009 05:18:38 +0000

Spondylarthritis (SpA) represents a group of arthritidies that share clinical features such as inflammatory back pain and inflammation at sites where tendons attach to bone. It includes ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel-disease-related arthritis, reactive arthritis (ReA) and undifferentiated spondylarthritides (uSpA). Since Chlamydia trachomatis or Chlamydia pneumoniae (which are often asymptomatic) frequently cause ReA, a new study examined whether there was a connection between these two infections and uSpA.

The study was published in the May issue of Arthritis & Rheumatism (http://www3.interscience.wiley.com/journal/76509746/home).

Led by John D. Carter of theUniversity of South Florida, the study involved blood and synovial tissue analysis from 26 patients who had chronic uSpA or Chlamydia-induced ReA. Synovial tissue samples from 167 osteoarthritis patients were used as controls. Samples were analyzed to assess chlamydial DNA and the 26 subjects were asked if they had any known exposure to Chlamydia trachomatis or Chlamydia pneumoniae and if so, the infection was documented in relation to the onset of their uSpA. They also underwent a physical exam that included evaluation of swollen and tender joints and other symptoms of SpA. The results showed that the rate of Chlamydiainfection was 62 percent in uSpA patients, significantly higher than the 12 percent seen in control subjects.

It is believed that as many as 150,000 cases of Chlamydia trachomatis-induced ReA may appear in the U.S. each year compared to about 125,000 new cases of rheumatoid arthritis. This is a low estimate since it does not include cases resulting from Chlamydia pneumoniae. “Thus, Chlamydia-induced ReA represents a considerable burden on the health care systems of the U.S. and other nations, and its impact on those systems may well be significantly under recognized,” the authors state.

Most women with genital Chlamydia trachomatis infection have no symptoms at the time of the initial infection; this was also true of the patients in the study who had DNA evidence of Chlamydia. For Chlamydia pneumoniae, as many as 70 percent of acute infections are asymptomatic and, even when there are symptoms, definitive identification of the organism is rare. The authors point out that relying on identification of a symptomatic infection may therefore result in routine underdiagnosis or misdiagnosis of Chlamydia-induced ReA.

They add that because ReA is a type of SpA and patients with ReA do not present with the classic combination of symptoms of arthritis, conjunctivitis/iritis and urethritis, it is reasonable to believe that Chlamydia trachomatis plays a role in causing uSpA, which may in fact be ReA. They conclude that although there is no diagnostic test for Chlamydia-induced ReA, testing for chlamydial DNA in the synovial tissue of patients thought to have ReA may be the most accurate way of diagnosing the condition.

Article: “Chlamydiae as Etiologic Agents in Chronic Undifferentiated Spondylarthritis,” John D. Carter, Hervé C. Gérard, Luis R. Espinoza, Louis R. Ricca, Joanne Valeriano, Jessica Snelgrove, Cynthia Oszust, Frank B. Vasey, Alan P. Hudson,Arthritis & Rheumatism, May 2009.

Microglia Are Mediators of Borrelia burgdorferi–Induced Apoptosis

Linda — Sat, 14 Nov 2009 22:06:20 +0000

Inflammation has long been implicated as a contributor to pathogenesis
in many CNS illnesses, including Lyme neuroborreliosis. Borrelia
burgdorferi is the spirochete that causes Lyme disease and it is known
to potently induce the production of inflammatory mediators in a variety
of cells. In experiments where B. burgdorferi was co-cultured in vitro
with primary microglia, we observed robust expression and release of
IL-6 and IL-8, CCL2 (MCP-1), CCL3 (MIP-1?), CCL4 (MIP-1?) and CCL5
(RANTES), but we detected no induction of microglial apoptosis. In
contrast, SH-SY5Y (SY) neuroblastoma cells co-cultured with B.
burgdorferi expressed negligible amounts of inflammatory mediators and
also remained resistant to apoptosis. When SY cells were co-cultured
with microglia and B. burgdorferi, significant neuronal apoptosis
consistently occurred. Confocal microscopy imaging of these cell
cultures stained for apoptosis and with cell type-specific markers
confirmed that it was predominantly the SY cells that were dying.
Microarray analysis demonstrated an intense microglia-mediated
inflammatory response to B. burgdorferi including up-regulation in gene
transcripts for TLR-2 and NF??. Surprisingly, a pathway that exhibited
profound changes in regard to inflammatory signaling was triggering
receptor expressed on myeloid cells-1 (TREM1). Significant transcript
alterations in essential p53 pathway genes also occurred in SY cells
cultured in the presence of microglia and B. burgdorferi, which
indicated a shift from cell survival to preparation for apoptosis when
compared to SY cells cultured in the presence of B. burgdorferi alone.
Taken together, these findings indicate that B. burgdorferi is not
directly toxic to SY cells; rather, these cells become distressed and
die in the inflammatory surroundings generated by microglia through a
bystander effect. If, as we hypothesized, neuronal apoptosis is the key
pathogenic event in Lyme neuroborreliosis, then targeting microglial
responses may be a significant therapeutic approach for the treatment of
this form of Lyme disease.
Author Summary

Lyme disease, which is transmitted to humans through the bite of a tick,
is currently the most frequently reported vector-borne illness in the
northern hemisphere. Borrelia burgdorferi is the bacterium that causes
Lyme disease and it is known to readily induce inflammation within a
variety of infected tissues. Many of the neurological signs and symptoms
that may affect patients with Lyme disease have been associated with B.
burgdorferi-induced inflammation in the central nervous system (CNS). In
this report we investigated which of the primary cell types residing in
the CNS might be functioning to create the inflammatory environment
that, in addition to helping clear the pathogen, could simultaneously be
harming nearby neurons. We report findings that implicate microglia, a
macrophage cell type in the CNS, as the key responders to infection with
B. burgdorferi. We also present evidence indicating that this organism
is not directly toxic to neurons; rather, a bystander effect is
generated whereby the inflammatory surroundings created by microglia in
response to B. burgdorferi may themselves be toxic to neuronal cells.

Citation: Myers TA, Kaushal D, Philipp MT (2009) Microglia Are Mediators
of Borrelia burgdorferi–Induced Apoptosis in SH-SY5Y Neuronal Cells.
PLoS Pathog 5(11): e1000659. doi:10.1371/journal.ppat.1000659

Editor: Jenifer Coburn, Medical College of Wisconsin, United States of
America

Received: May 11, 2009; Accepted: October 19, 2009; Published: November
13, 2009

Copyright: © 2009 Myers et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.

Funding: This work was supported by grants NS048952 and RR00164 from the
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.

Competing interests: The authors have declared that no competing
interests exist.

Full text available at this URL

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000659

Microglia Are Mediators of Borrelia burgdorferi–Induced Apoptosis in
SH-SY5Y Neuronal Cells

Tereance A. Myers, Deepak Kaushal, Mario T. Philipp*

Division of Bacteriology & Parasitology, Tulane National Primate
Research Center, Tulane University Health Sciences Center, Louisiana,
United States of America

Abstract

inflammatory – F.I.G.H.T for your health!

Chlamydia May Play Role In a Type of Arthritis

Microglia Are Mediators of Borrelia burgdorferi–Induced Apoptosis