Excerpt:

The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

Excerpt:

The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

Excerpt:

A landmark paper on homeopathy and cancer has appeared in the February 2010 issue of the International Journal of Oncology. Scientists at the University of Texas M.D. Anderson Cancer Center (MDA), led by Moshe Frenkel, MD, have confirmed the ability of four homeopathic remedies to induce apoptosis (programmed cell death) in breast cancer cell lines in the laboratory. The scientists in question were from the Integrative Medicine Program, the Department of Molecular Pathology, and the Department of Melanoma Medical Oncology of MDA. Their two Indian collaborators were from the Banerji Homeopathic Research Foundation, Kolkata, India, where these same remedies are employed clinically with apparent success. The four ultra-dilute remedies in question were Carcinosin, Phytolacca, Conium and Thuja.

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