Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat."

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Latent virus and life expectancy: Virus shortens telomeres - Medical News Today

The telomeres are repetitive DNA sequences at each end of our chromosomes. Studies show that in every cell division, the telomere is shortened. As a result, the telomere limits the cell to a fixed number of divisions and a limited life span. An essential part of human cells they affect how our cells age - as people with longer telomeres live longer lives. Surprisingly, people who are infected with a latent virus, that is, an asymptomatic virus, have shorter telomeres. This is an important observation and a great mystery. Is the virus causing the telomere shortening, and how? And if this is the case, what does it mean in terms of the relationship between the latent viruses and longevity?
Now, an article "The Latent Cytomegalovirus Decreases Telomere Length By Microcompetition" by Hanan Polansky and Adrian Javaherian, published in Open Medicine by De Gruyter Open, provides some answers to these questions. As it turns out, a certain gene, called telomere repeat binding factor 2 (Terf2), belongs to a complex of six telomere-associated proteins, termed shelterin. The protein produced by this gene protects the chromosome ends of the DNA from damage, and controls telomere maintenance by the telomerase enzyme. When does a cell produce the Terf2 protein? After receiving a signal that tells a transcription factor called GABP to bind the Terf2 gene. One can think of GABP as a finger that pushes the "ON" button on the Terf2 gene. Now consider a case where a latent virus called CMV infects the cell. As it turns out, the CMV virus also uses the GABP transcription factor to press the "ON" button on its own genes. When the CMV virus steals the GABP "fingers" from the Terf2 gene, there are no fingers left to press the "ON" button on the Terf2 gene, and the Terf2 gene fails to produce the Terf2 protein. What is the result of a shortage of Terf2 proteins? Short telomeres. In his book "Microcompetition with Foreign DNA and the Origin of Chronic Disease", Dr. Polansky used the term Microcompetition to describe this event.

Can autism be measured in a sniff?

Imagine the way you might smell a rose. You'd take a nice big sniff to breathe in the sweet but subtle floral scent. Upon walking into a public restroom, you'd likely do just the opposite—abruptly limiting the flow of air through your nose. Now, researchers reporting in the Cell Press journal Current Biology on July 2 have found that people with autism spectrum disorder (ASD) don't make this natural adjustment like other people do. Autistic children go right on sniffing in the same way, no matter how pleasant or awful the scent.

Here's the paper:-

Mechanistic Link between Olfaction and Autism Spectrum Disorder

Stealth Adapted Viruses – Possible Drivers of Major Neuropsychiatric Illnesses Including Alzheimer’s Disease

Mainstream neurologists and psychiatrists have largely refrained from serious
consideration of a virus cause of common brain diseases. This is mainly because
of the general lack of any accompanying immune system stimulated inflammatory reaction within the brain. This article exposes a weakness in this argument by describing the process of “stealth adaptation” of viruses. Deletion or mutation of relatively few virus components can result in derivative viruses, which are no longer effectively recognized by the cellular immune system. Consequently, there is no triggering of the inflammatory response. Furthermore, the brain is uniquely susceptible to symptomatic illness caused by stealth adapted viruses.
An understanding of stealth adaptation greatly expands the potential scope of
viral illnesses. It also underscores the value of using virus cultures as a diagnostic tool and of taking appropriate measures to avoid transmission of infection. More
importantly, therapeutic measures are available for suppressing both stealth
adapted and conventional virus infections through enhancement of the alternative
cellular energy (ACE) pathway. Such measures are available for clinical evaluation in treating many of the major illnesses affecting the brain, including Alzheimer’s

Immune response to a flu protein yields new insights into narcolepsy

An international team of researchers has found some of the first solid
evidence that narcolepsy may be a so-called "hit-and-run" autoimmune

The authors propose a hit-and-run autoimmune mechanism for how both
swine flu and the vaccine Pandemrix might cause narcolepsy. They suggest that in
genetically predisposed people, high levels of the H1N1 protein
stimulate the production of large amounts of antibodies to both the
virus (or vaccine) and the hypocretin receptor. These antibodies may persist in the
blood for months. Either the large numbers of antibodies or inflammation
from an unrelated infection could alter the blood-brain barrier,
allowing the antibodies to enter the brain. There, the antibodies may
latch onto hypocretin receptors, possibly directing the immune system to
destroy or suppress brain cells critical to regulating sleep-wake

Omega-3 supplements, antioxidants may help with preclinical Alzheimer's disease: Clinical trials of omega-3, antioxidant supplementation should be undertaken for people with Alzheimer's disease with mild clinical impairment -- ScienceDaily

Here's more evidence that fish oil supplementation and antioxidants might be beneficial for at least some people facing Alzheimer's disease: A new report published in the July 2015 issue of The FASEB Journal describes the findings of a very small study in which people with mild clinical impairment, such as those in the very early stages of the disease, saw clearance of the hallmark amyloid-beta protein and reduced inflammation in neurological tissues. Although the findings involved just 12 patients over the course of 4 to 17 months, the findings suggest further clinical study of this relatively inexpensive and plentiful supplement should be conducted.

Parkinson's disease may begin in the gut

New research indicates that Parkinson's disease may begin in the gastrointestinal tract and spread through the vagus nerve to the brain.

We have conducted a registry study of almost 15,000 patients
who have had the vagus nerve in their stomach severed. Between
approximately 1970-1995 this procedure was a very common method of ulcer
treatment. If it really is correct that Parkinson's starts in the gut
and spreads through the vagus nerve, then these vagotomy patients should
naturally be protected against developing Parkinson's disease,"
explains postdoc at Aarhus University Elisabeth Svensson on the
hypothesis behind the study.
"The study shows that patients who have had the the entire vagus
nerve severed were protected against Parkinson's disease. Their risk was
halved after 20 years. However, patients who had only had a small part
of the vagus nerve severed where not protected. This also fits the
hypothesis that the disease process is strongly dependent on a fully or
partially intact vagus nerve to be able to reach and affect the brain,"
she says.
The research project has just been published in the internationally recognised journal Annals of Neurology.

Herpes simplex virus type 2 infection induces AD-like neurodegeneration markers in human neuroblastoma cells - Neurobiology of Aging

Herpes simplex virus (HSV) types 1 and 2 are neurotropic viruses that
establish lifelong latent infections in neurons. Mounting evidence
suggests that HSV-1 infection is involved in the pathogenesis of
Alzheimer’s disease (AD). The relationships between other herpesvirus
infections and events associated with neurodegeneration have not,
however, been extensively studied. The present work reports that HSV-2
infection leads to the strong accumulation of hyperphosphorylated tau
and the amyloid-β peptides Aβ40 and Aβ42 (all major pathological
hallmarks of AD) in human SK-N-MC neuroblastoma cells. Infection is also
associated with a marked reduction in the amount of Aβ40 secreted, and
in the proteolytic fragments of the amyloid-β precursor protein (APP)
(secreted APPα and the α-C-terminal fragment). These results indicate
that HSV-2 infection inhibits the non-amyloidogenic pathway of APP
processing and impairs Aβ secretion in these cells. In addition, HSV-2
induces the accumulation of intracellular autophagic compartments
containing Aβ due to a failure in the late stages of autophagy. To our
knowledge, this is the first report to show that HSV-2 infection
strongly alters the tau phosphorylation state, APP processing, and
autophagic process in human neuroblastoma cells, leading to the
appearance of AD-like neurodegeneration markers.

Epstein-Barr virus genetic variants are associated with multiple sclerosis. - PubMed - NCBI


We analyzed the Epstein-Barr nuclear antigen 2 (EBNA2) gene, which
contains the most variable region of the viral genome, in persons with
multiple sclerosis (MS) and control subjects to verify whether virus
genetic variants are involved in disease development.


A seminested PCR approach and Sanger sequencing were used to analyze
EBNA2 in 53 patients and 38 matched healthy donors (HDs).
High-throughput sequencing by Illumina MiSeq was also applied in a
subgroup of donors (17 patients and 17 HDs). Patients underwent
gadolinium-enhanced MRI and human leucocyte antigen typing.


risk significantly correlated with an excess of 1.2 allele (odds ratio
[OR] = 5.13; 95% confidence interval [CI] 1.84-14.32; p = 0.016) and
underrepresentation of 1.3B allele (OR = 0.23; 95% CI 0.08-0.51; p =
0.0006). We identified new genetic variants, mostly 1.2 allele- and
MS-associated (especially amino acid variation at position 245; OR =
9.4; 95% CI 1.19-78.72; p = 0.0123). In all cases, the consensus
sequence from deep sequencing confirmed Sanger sequencing (including the
cosegregation of newly identified variants with known EBNA2 alleles)
and showed that the extent of genotype intraindividual variability was
higher than expected: rare EBNA2 variants were detected in all HDs and
patients with MS (range 1-17 and 3-19, respectively). EBNA2 variants did
not seem to correlate with human leucocyte antigen typing or
clinical/MRI features.


Our study unveils a strong association between Epstein-Barr virus genomic
variants and MS, reinforcing the idea that Epstein-Barr virus
contributes to disease development.

Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination.

Clostridium perfringens epsilon toxin (ε-toxin) is responsible for a devastating multifocal central nervous system (CNS) white matter disease in ruminant animals. The mechanism by which ε-toxin causes white matter damage is poorly understood. In this study, we sought to determine the molecular and cellular mechanisms by which ε-toxin causes pathological changes to white matter. In primary CNS cultures, ε-toxin binds to and kills oligodendrocytes but not astrocytes, microglia, or neurons. In cerebellar organotypic culture, ε-toxin induces demyelination, which occurs in a time- and dose-dependent manner, while preserving neurons, astrocytes, and microglia. ε-Toxin specificity for oligodendrocytes was confirmed using enriched glial culture. Sensitivity to ε-toxin is developmentally regulated, as only mature oligodendrocytes are susceptible to ε-toxin; oligodendrocyte progenitor cells are not. ε-Toxin sensitivity is also dependent on oligodendrocyte expression of the proteolipid myelin and lymphocyte protein (MAL), as MAL-deficient oligodendrocytes are insensitive to ε-toxin. In addition, ε-toxin binding to white matter follows the spatial and temporal pattern of MAL expression. A neutralizing antibody against ε-toxin inhibits oligodendrocyte death and demyelination. This study provides several novel insights into the action of ε-toxin in the CNS. (i) ε-Toxin causes selective oligodendrocyte death while preserving all other neural elements. (ii) ε-Toxin-mediated oligodendrocyte death is a cell autonomous effect. (iii) The effects of ε-toxin on the oligodendrocyte lineage are restricted to mature oligodendrocytes. (iv) Expression of the developmentally regulated proteolipid MAL is required for the cytotoxic effects. (v) The cytotoxic effects of ε-toxin can be abrogated by an ε-toxin neutralizing antibody.


Our intestinal tract is host to trillions of microorganisms that play an essential role in health and homeostasis. Disruption of this symbiotic relationship has been implicated in influencing or causing disease in distant organ systems such as the brain. Epsilon toxin (ε-toxin)-carrying Clostridium perfringens strains are responsible for a devastating white matter disease in ruminant animals that shares similar features with human multiple sclerosis. In this report, we define the mechanism by which ε-toxin causes white matter disease. We find that ε-toxin specifically targets the myelin-forming cells of the central nervous system (CNS), oligodendrocytes, leading to cell death.
The selectivity of ε-toxin for oligodendrocytes is remarkable, as other cells of the CNS are unaffected. Importantly, ε-toxin-induced oligodendrocyte death results in demyelination and is dependent on expression of myelin and lymphocyte protein (MAL). These results help complete the mechanistic pathway from bacteria to brain by explaining the specific cellular target of ε-toxin within the CNS.

Fructose powers a vicious circle -- ScienceDaily

A new paper by Krek and his team member Peter Mirtschink describes a
further, more troubling side effect of fructose. The researchers have
discovered a previously unknown molecular mechanism that points to
fructose as a key driver of uncontrolled growth of the heart muscle, a
condition that can lead to fatal heart failure. Their study was recently
published in Nature.

When a person has high blood pressure, the heart has to grow as it is
harder to pump the blood through the circulatory system. These growing
heart muscle cells require a considerable amount of oxygen. However,
since not enough oxygen is available to adequately supply the increased
growth, the cells switch to an alternative energy supply. Instead of
drawing energy from fatty acids, they rely more on an anaerobic process
called glycolysis -- literally, the 'splitting of sugars'. If the heart
muscle cells can access fructose in addition to glucose, this can set
off a fatal chain reaction.

The genes of the ocean microbiome are similar to those of human gut microbiota | AGÊNCIA FAPESP

By analyzing the 7.2 Tb of metagenomic data from these 243 bacterial samples, Sarmento and fellow researchers in the consortium generated an ocean microbial reference gene catalogue with more than 40 million genes. Based on the catalogue, which is publicly available on the internet for use by the scientific community free of charge, the researchers identified a core set of gene families that are the most common in marine microorganisms.

A comparison with the genes sequenced by the Human Microbiome Project and MetaHIT shows that over 73% of the functional genes in marine microorganisms are shared with the human gut microbiome, despite the physicochemical differences between these two ecosystems. “Genetic sequencing of the plankton samples collected during the expedition could result in the identification of tens of thousands of new species of bacteria, single-cell organisms and marine viruses,” Sarmento said.

Prenatal DDT exposure tied to nearly four-fold increase in breast cancer risk

Women who were exposed to higher levels of the pesticide DDT in utero were nearly four times more likely to be diagnosed with breast cancer as adults than women who were exposed to lower levels before birth, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology and Metabolism (JCEM). A more estrogenic form of DDT that is found in commercial DDT, o,p'-DDT, was largely responsible for this finding.

Selective damage to dopaminergic transporters following exposure to the brominated flame retardant, HBCDD

Over the last several decades, the use of halogenated organic compounds
has become the cause of environmental and human health concerns. Of
particular notoriety has been the establishment of the neurotoxicity of
polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers
(PBDEs). The subsequent banning of PBDEs has led to greatly increased
use of 1,2,5,6,9,10-hexabromocyclododecane (HBCDD, also known as HBCD)
as a flame retardant in consumer products. The physiochemical
similarities between HBCDD and PBDEs suggest that HBCDD may also be
neurotoxic to the dopamine system, which is specifically damaged in
Parkinson disease (PD). The purpose of this study was to assess the
neurotoxicity of HBCDD on the nigrostriatal dopamine system using an in
vitro and in vivo approach. We demonstrate that exposure to HBCDD
(0-25μM) for 24hrs causes significant cell death in the SK-N-SH
catecholaminergic cell line, as well as reductions in the growth and
viability of TH+ primary cultured neurons at lower concentrations
(0-10μM) after 72hrs of treatment. Assessment of the in vivo
neurotoxicity of HBCDD (25mg/kg for 30days) resulted in significant
reductions in the expression of the striatal dopamine transporter and
vesicular monoamine transporter 2, both of which are integral in
mediating dopamine homeostasis and neurotransmission in the dopamine
circuit. However, no changes were seen in the expression of tyrosine
hydroxylase in the dopamine terminal, or striatal levels of dopamine. To
date, these are the first data to demonstrate that exposure to HBCDD
disrupts the nigrostriatal dopamine system. Given these results and the
ubiquitous nature of HBCDD in the environment, its possible role as an
environmental risk factor for PD should be further investigated.

Vulnerability of synapses in the frontal cortex of mice developmentally exposed to an insecticide: Potential contribution to neuropsychiatric disease. - PubMed - NCBI

Increasingly, exposure to various chemicals found in our environment has
been found to be a significant contributor to the risk of developing
neurological disease, such as Parkinson disease, autism spectrum
disorder, as well as other deficits in thought and function. Exposure to
these compounds during critical periods of neurodevelopment,
encompassing exposures that occur in utero, during infancy,
childhood, and adolescence, represents a time period of nervous system
growth that is uniquely vulnerable to disruption by environmental
chemicals. Indeed, a contemporary hypothesis suggests that the
pathological cascade associated with many common neurological disorders
has its origin in disturbances of normal neurodevelopment. Moreover,
alterations to the ontogeny of the synapse and neurotransmitter
signaling during neurodevelopment may be a premier pathological event
that underlies neuropsychiatric and neurodegenerative disease. To
interrogate the impact of exposure to a ubiquitous environmental
chemical, the pesticide, endosulfan, on development of neurotransmitter
circuits, we coupled in vitro and in vivo platforms to
evaluate its effect on the formation of GABAergic, glutamatergic, and
dopaminergic pathways in the frontal cortex. With this approach we found
exposure of cortical neurons, in vitro, exhibited a marked
reduction in the length of their neurite process as well as the number
of synaptic connections. Further investigation using an in vivo
model of developmental exposure identified significant alterations to
pre and postsynaptic proteins involved in neurotransmitter handling and
signaling in each of the neurotransmitter systems investigated. These
findings suggest that exposure to endosulfan during vulnerable periods
of neurodevelopment can alter the normal development and potential
function of neurotransmission in the frontal cortex. Interestingly, the
alterations identified in our study closely mimic the pathological
markers associated with schizophrenia, which shows disturbances in
synaptic proteins important for GABAergic, glutamatergic, and
dopaminergic signaling in the frontal cortex. These findings provide
important support for the impact of exposure to environmental chemicals
during neurodevelopment and risk for neurological disease.

Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer's Disease. - PubMed - NCBI

Periodontal disease (PD) and Alzheimer's disease (AD) are inflammatory
conditions affecting the global adult population. In the pathogenesis of
PD, subgingival complex bacterial biofilm induces inflammation that
leads to connective tissue degradation and alveolar bone resorption
around the teeth. In health, junctional epithelium seals the gingiva to
the tooth enamel, thus preventing bacteria from entering the gingivae.
Chronic PD involves major pathogens (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia)
which have an immune armoury that can circumvent host's immune
surveillance to create and maintain an inflammatory mediator rich and
toxic environment to grow and survive. The neurodegenerative condition,
AD, is characterised by poor memory and specific hallmark proteins;
periodontal pathogens are increasingly being linked with this dementing
condition. It is therefore becoming important to understand associations
of periodontitis with relevance to late-onset AD. The aim of this
review is to discuss the relevance of finding the keystone periodontal
pathogen P. gingivalis in AD brains and its plausible contribution to the aetiological hypothesis of this dementing condition.

Immune alterations in acute bipolar depression. - PubMed - NCBI


Immunologic abnormalities have been found in bipolar disorder and acute mania.
However, there have been fewer studies of patients with acute bipolar


Blood samples were obtained from individuals with acute bipolar depression,
acute mania, and controls. These samples were evaluated for antibodies
to human herpesviruses, gliadin, Toxoplasma gondii, and endogenous
retroviruses as well as for C-reactive protein (CRP) and pentraxin-3
using immunoassay methods. Linear regression models were used to compare
the levels of the markers controlling for demographic and clinical
variables. A subset of the bipolar depressed group was evaluated at a
6-month follow-up.


The sample consisted of 82 individuals with acute bipolar depression, 147
with acute mania, and 280 controls. The levels of CRP and IgG antibodies
to an endogenous retrovirus, Mason-Pfizer monkey virus (MPMV), were
significantly elevated in the bipolar depressed group. Levels of
pentraxin-3 were reduced in both psychiatric groups. An evaluation of 32
individuals 6 months after hospitalization for bipolar depression
showed a significant decrease in the levels of MPMV antibodies, but not a
change in the other markers.


Individuals with acute bipolar depression show immune alterations. Some of the
alterations are similar to those found in acute mania.

Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother–child cohort

Pyrethroid insecticides are widely used in agriculture
and in homes. Despite the neurotoxicity of these insecticides at high
doses, few studies have examined whether lower-level exposures could
adversely affect children's neurodevelopment.
The PELAGIE cohort included 3421 pregnant women from Brittany, France
between 2002 and 2006. When their children reached their sixth birthday,
428 mothers from the cohort were randomly selected, successfully
contacted and found eligible. A total of 287 (67%) mothers agreed to
participate with their children in the neuropsychological follow-up. Two
cognitive domains were assessed by the Wechsler Intelligence Scale for
Children: verbal comprehension and working memory. Five pyrethroid and
two organophosphate insecticide metabolites were measured in maternal
and child first-void urine samples collected between 6 and 19
gestational weeks and at 6 years of age, respectively. Linear regression
models were used to estimate associations between cognitive scores and
urinary pyrethroid metabolite concentrations, adjusting for
organophosphate metabolite concentrations and potential confounders.
Maternal prenatal pyrethroid metabolite concentrations were not consistently
associated with any children's cognitive scores. By contrast, childhood
3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend = 0.04 and P-trend < 0.01, respectively) and with working memory scores (P-trend = 0.05 and P-trend < 0.01,
respectively). No associations were observed for the three other
childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA).
Low-level childhood exposures to deltamethrin (as cis-DBCA
is its principal and selective metabolite), in particular, and to
pyrethroid insecticides, in general (as reflected in levels of the 3-PBA
metabolite) may negatively affect neurocognitive development by 6 years
of age. Whatever their etiology, these cognitive deficits may be of
importance educationally, because cognitive impairments in children
interfere with learning and social development. Potential causes that
can be prevented are of paramount public health importance.