PolygenicBlog

Immuno-microbiota cross and talk: The new paradigm of metabolic diseases.

noreply@blogger.com (Chris Carter) — Sun, 29 Jan 2012 08:32:38 PST

Over the last decades the rising occurrence of metabolic diseases throughout the world points to the failure of preventive and therapeutic strategies and of the corresponding molecular and physiological concepts. Therefore, a new paradigm needs to be elucidated. Very recently the intimate cross talk of the intestinal microbiota with the host immune system has opened new avenues. The large diversity of the intestinal microbes' genome, i.e. the metagenome, and the extreme plasticity of the immune system provide a unique balance which, when finely tuned, maintains a steady homeostasis. The discovery that a new microbiota repertoire is one of the causes responsible for the onset of metabolic disease suggests that the relationship with the immune system is impaired. Therefore, we here review the recent arguments that support the view that an alteration in the microbiota to host immune system balance leads to an increased translocation of bacterial antigens towards metabolically active tissues, and could result in a chronic inflammatory state and consequently impaired metabolic functions such as insulin resistance, hepatic fat deposition, insulin unresponsiveness, and excessive adipose tissue development. This imbalance could be at the onset of metabolic diseas, and therefore the early treatment of the microbiota dysbiosis or immunomodulatory strategies should prevent and slow down the epidemic of metabolic diseases and hence the corresponding lethal cardiovascular consequences.

Microbiota in autoimmunity and tolerance.

noreply@blogger.com (Chris Carter) — Sun, 29 Jan 2012 08:30:52 PST

The composition of a host's intestinal microbiota directs the type of mucosal and systemic immune responses by affecting the proportion and number of functionally distinct T cell subsets. In particular, the microbiota composition affects the differentiation of intestinal Th17 cells and Foxp3(+) regulatory T cells, both of which play critical roles in maintaining mucosal barrier functions and in controlling immunological homeostasis. In this review, we discuss the recent advances in our understanding of how the intestinal microbiota affects T cell differentiation and host susceptibility to autoimmune disease.

Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active Multiple Sclerosis.

noreply@blogger.com (Chris Carter) — Sat, 28 Jan 2012 14:00:54 PST

Multiple Sclerosis (MS) is considered to be an autoimmune disease with unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS.Human Endogenous Retroviruses (HERVs) constitute 5-8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. The HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS.The authors studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in PBMCs from healthy controls and from MS patients with non-active or active disease. There was a significant increase in HERV-H/F Gag expression in CD4+ (P<0.001***) and CD8+ T lymphocytes (P<0.001***), and in monocytes (P=0.0356*) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute Q-PCR evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We have found a 4 fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS as compared with healthy controls (P<0.001***). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expressions will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.

Antiviral CD8(+) T cells cause an experimental autoimmune encephalomyelitis-like disease in naive mice.

noreply@blogger.com (Chris Carter) — Sat, 28 Jan 2012 10:01:30 PST

Major histocompatibility complex class I-restricted CD8(+) cytotoxic T lymphocytes are involved in the pathogenesis of multiple sclerosis (MS) and both autoimmune, experimental autoimmune encephalomyelitis, and viral, Theiler's murine encephalomyelitis virus (TMEV) infection, animal models of MS. Following TMEV infection, certain T cell hybridomas, generated from cloned TMEV-induced CD8(+) T cells, were able to produce clinical signs of disease (flaccid hind limb paralysis) upon adoptive transfer into naive mice. Dual T cell receptors (TCR) are present on the surface of these cells as both Vβ3 and Vβ6 were detected by polymerase chain reaction (PCR) screening and flow cytometry and multiple Vα mRNAs were detected by PCR screening. This is the first demonstration of antiviral CD8(+) T cells having more than one TCR initiating an autoimmune disease in the natural host of the virus. We hypothesize that this is a potential mechanism for virus-induced autoimmune disease initiated by CD8(+) T cells.

Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress

noreply@blogger.com (Chris Carter) — Sat, 28 Jan 2012 05:47:18 PST

Chronic fatigue syndrome (CFS) is a complex illness, which is often misdiagnosed as a psychiatric illness. In two previous reports, using (1) H MRSI, we found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in patients with CFS relative to those with generalized anxiety disorder and healthy volunteers (HV), but not relative to those with major depressive disorder (MDD). In this third independent cross-sectional neuroimaging study, we investigated a pathophysiological model which postulated that elevations of CSF lactate in patients with CFS might be caused by increased oxidative stress, cerebral hypoperfusion and/or secondary mitochondrial dysfunction. Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the following modalities: (i) (1) H MRSI to measure CSF lactate; (ii) single-voxel (1) H MRS to measure levels of cortical glutathione (GSH) as a marker of antioxidant capacity; (iii) arterial spin labeling (ASL) MRI to measure regional cerebral blood flow (rCBF); and (iv) (31) P MRSI to measure brain high-energy phosphates as objective indices of mitochondrial dysfunction. We found elevated ventricular lactate and decreased GSH in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD. We found no differences between the three groups in terms of any high-energy phosphate metabolites. In exploratory correlation analyses, we found that levels of ventricular lactate and cortical GSH were inversely correlated, and significantly associated with several key indices of physical health and disability. Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology. Copyright © 2012 John Wiley & Sons, Ltd.

PLoS Pathogens: The Circadian Clock Protein Timeless Regulates Phagocytosis of Bacteria in Drosophila

noreply@blogger.com (Chris Carter) — Sat, 28 Jan 2012 00:42:30 PST

Survival of bacterial infection is the result of complex host-pathogen interactions. An often-overlooked aspect of these interactions is the circadian state of the host. Previously, we demonstrated that Drosophila mutants lacking the circadian regulatory proteins Timeless (Tim) and Period (Per) are sensitive to infection by S. pneumoniae. Sensitivity to infection can be mediated either by changes in resistance (control of microbial load) or tolerance (endurance of the pathogenic effects of infection). Here we show that Tim regulates resistance against both S. pneumoniae and S. marcescens. We set out to characterize and identify the underlying mechanism of resistance that is circadian-regulated. Using S. pneumoniae, we found that resistance oscillates daily in adult wild-type flies and that these oscillations are absent in Tim mutants. Drosophila have at least three main resistance mechanisms to kill high levels of bacteria in their hemolymph: melanization, antimicrobial peptides, and phagocytosis. We found that melanization is not circadian-regulated. We further found that basal levels of AMP gene expression exhibit time-of-day oscillations but that these are Tim-independent; moreover, infection-induced AMP gene expression is not circadian-regulated. We then show that phagocytosis is circadian-regulated. Wild-type flies exhibit up-regulated phagocytic activity at night; Tim mutants have normal phagocytic activity during the day but lack this night-time peak. Tim appears to regulate an upstream event in phagocytosis, such as bacterial recognition or activation of phagocytic hemocytes. Interestingly, inhibition of phagocytosis in wild type flies results in survival kinetics similar to Tim mutants after infection with S. pneumoniae. Taken together, these results suggest that loss of circadian oscillation of a specific immune function (phagocytosis) can have significant effects on long-term survival of infection.

Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination.

noreply@blogger.com (Chris Carter) — Fri, 27 Jan 2012 04:09:10 PST

Commensal gut flora-in the absence of pathogenic agents-is essential in triggering immune processes, leading to a relapsing-remitting autoimmune disease driven by myelin-specific CD4(+) T cells.

MicrobeWorld - Viruses con bacteria into working for them

noreply@blogger.com (Chris Carter) — Fri, 27 Jan 2012 04:05:33 PST

These viruses are carrying genetic material taken from their previous bacterial hosts that tricks the new host into using its own machinery to activate the genes:

IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways in inflammatory and neuroprogressive pathology

noreply@blogger.com (Chris Carter) — Fri, 27 Jan 2012 02:58:04 PST

Depression is characterized by IgM-related autoimmune responses directed against a) neoepitopes that are normally not detected by the immune system but that due to damage by oxidative and nitrosative stress have become immunogenic; and b) anchorage epitopes, i.e. palmitic and myristic acids, and S-farnesyl-L-cysteine. These autoimmune responses play a role in the inflammatory and oxidative and nitrosative stress pathophysiology of depression and may mediate the cellular dysfunctions that contribute to neuroprogression, e.g. aberrations in signal transduction, cellular differentiation and apoptosis.

Measles IgG antibody index correlates with t2 lesion load on MRI in patients with early multiple sclerosis.

noreply@blogger.com (Chris Carter) — Fri, 27 Jan 2012 02:54:01 PST

B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS). A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR). Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs) of MRZR with magnetic resonance imaging (MRI) findings in patients with first MS diagnosis.
Multiple sclerosis

How viruses evolve, and in some cases, become deadly

noreply@blogger.com (Chris Carter) — Fri, 27 Jan 2012 02:38:49 PST

Researchers at Michigan State University (MSU) have demonstrated how a new virus evolves, shedding light on how easy it can be for diseases to gain dangerous mutations. The findings appear in the current issue of the journal Science.

Scientists map one of life's molecular mysteries: Visualisation of the molecular gateway across and into cellular membranes

noreply@blogger.com (Chris Carter) — Fri, 27 Jan 2012 02:37:20 PST

All living organisms are made up of cells, behind these intricate life forms lie complex cellular processes that allow our bodies to function. Researchers working on protein secretion -- a fundamental process in biology -- have revealed how protein channels in the membrane are activated by special signals contained in proteins destined for secretion. The results help explain the underlying mechanism responsible for the release of proteins such as hormones and antibodies into the blood stream.

De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 23:35:41 PST

In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case copy number variations were enriched for members of the NMDAR complex (P=0.0015) but not ARC (P=0.14). Our data indicate that defects in NMDAR postsynaptic signalling and, possibly, neuronal activity-regulated cytoskeleton-associated protein (ARC) complexes, which are known to be important in synaptic plasticity and cognition, play a significant role in the pathogenesis of schizophrenia.

Mutation drives viral sensors to initiate autoimmune disease

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 23:09:23 PST

A new study uses a mouse model of a human autoimmune disease to reveal how abnormal regulation of the intracellular sensors that detect invading viruses can lead to autoimmune pathology. The research, published online on January 26th in the journal Immunity by Cell Press, provides key insight into mechanisms that underlie the development of autoimmune disease and may lead to more effective strategies for therapeutic intervention.

Elevated risk factors linked to major cardiovascular disease events across a lifetime, January 25, 2012 News Release - National Institutes of Health (NIH)

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 13:29:13 PST

This National Institutes of Health-supported study used health data from 257,384 people and was the first to look simultaneously at multiple risk factors for cardiovascular disese across age, sex, race, and birth generation.The risk equates to a summation of effects, many of which are avoidable.

Survey of pet dogs indicates Lyme disease risk much greater than previous estimates suggest

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 12:37:41 PST

Ticks infected with the bacteria (Borrelia burgdorferi) that cause Lyme disease may be considerably more prevalent in the UK than expected, according to new research from the University of Bristol that used pet dogs as ‘sentinels’ for human disease risk.

The common immunogenic etiology of chronic fatigue syndrome: from infections to vaccines via adjuvants to the ASIA syndrome.

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 12:09:19 PST

Chronic fatigue syndrome is characterized by unexplained fatigue that lasts for at least 6 months with a constellation of other symptoms. Most cases start suddenly, and are usually accompanied by a flu-like illness. It is a symptom-based diagnosis of exclusion, the pathogenesis of which is unknown. Studies have examined and hypothesized about the possible biomedical and epidemiologic characteristics of the disease, including genetic predisposition, infections, endocrine abnormalities, and immune dysfunction and psychological and psychosocial factors. Recently, the AISA (autoimmune/inflammatory syndrome induced by adjuvants) syndrome was recognized, indicating the possible contribution of adjuvants and vaccines to the development of autoimmunity.

Brown Fat Burns Ordinary Fat, Study Finds - NYTimes.com

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 08:05:11 PST

Image via Wikipedia

Brown Fat, Triggered by Cold or Exercise, May Yield a Key to Weight Control (or excercise in a cold room !)

Manufacturing chemicals may damage the immune system : Nature News & Comment

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 07:17:27 PST

Perfluorinated compounds are used in food packaging and industrial manufacturing. A study in the Journal of the American Medical Association now shows that elevated levels of these chemicals in human blood are associated with a threefold increase in the risk of vaccines failing to protect against diseases such as tetanus

Diabetes Mystery: Why Are Type 1 Cases Surging?: Scientific American

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 07:14:18 PST

For reasons that are completely mysterious, however, the incidence of type 1 diabetes has been increasing throughout the globe at rates that range from 3 to 5 percent a year. Although the second trend is less well publicized, it is still deeply troubling, because this form of the illness has the potential to disable or kill people so much earlier in their lives.

Entry point for hepatitis C infection identified

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 06:16:08 PST

A molecule embedded in the membrane of human liver cells that aids in cholesterol absorption also allows the entry of hepatitis C virus, the first step in hepatitis C infection, according to research at the University of Illinois at Chicago College of Medicine. knocking down or blocking access to the NPC1L1 receptor prevented the virus from entering and infecting cells. This receptor (Niemann-Pick disease, type C1, gene)-like 1) is involved in cholesterol/lipoprotein physiology and also takes up Vitamin E.

High animal fat diet increases gestational diabetes risk, study finds

noreply@blogger.com (Chris Carter) — Thu, 26 Jan 2012 03:26:36 PST

Women who consumed a diet high in animal fat and cholesterol before pregnancy were at higher risk for gestational diabetes than women whose diets were lower in animal fat and cholesterol, according to researchers at the National Institutes of Health and Harvard University.

Genetic variation increases risk of metabolic side effects in children on some antipsychotics

noreply@blogger.com (Chris Carter) — Wed, 25 Jan 2012 03:57:16 PST

The variant was in MTHFR (methylenetetrahydrofolate reductase)

High levels of fructose consumption by adolescents may put them at cardiovascular risk, evidence suggests

noreply@blogger.com (Chris Carter) — Wed, 25 Jan 2012 03:48:55 PST

Evidence of cardiovascular disease and diabetes risk is present in the blood of adolescents who consume a lot of fructose, a scenario that worsens in the face of excess belly fat, researchers report.
Childhood obesity risk factors

Food fried in olive or sunflower oil is not linked to heart disease, Spanish study finds

noreply@blogger.com (Chris Carter) — Wed, 25 Jan 2012 03:45:04 PST

Eating food fried in olive or sunflower oil is not linked to heart disease or premature death, finds a paper published in the British Medical Journal online

PolygenicBlog

Immuno-microbiota cross and talk: The new paradigm of metabolic diseases.

Microbiota in autoimmunity and tolerance.

Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active Multiple Sclerosis.

Antiviral CD8(+) T cells cause an experimental autoimmune encephalomyelitis-like disease in naive mice.

Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress

PLoS Pathogens: The Circadian Clock Protein Timeless Regulates Phagocytosis of Bacteria in Drosophila

Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination.

Related articles

MicrobeWorld - Viruses con bacteria into working for them

IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways in inflammatory and neuroprogressive pathology

Measles IgG antibody index correlates with t2 lesion load on MRI in patients with early multiple sclerosis.

Related articles

How viruses evolve, and in some cases, become deadly

Scientists map one of life's molecular mysteries: Visualisation of the molecular gateway across and into cellular membranes

De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia

Mutation drives viral sensors to initiate autoimmune disease

Elevated risk factors linked to major cardiovascular disease events across a lifetime, January 25, 2012 News Release - National Institutes of Health (NIH)

Survey of pet dogs indicates Lyme disease risk much greater than previous estimates suggest

The common immunogenic etiology of chronic fatigue syndrome: from infections to vaccines via adjuvants to the ASIA syndrome.

Related articles

Brown Fat Burns Ordinary Fat, Study Finds - NYTimes.com

Brown Fat, Triggered by Cold or Exercise, May Yield a Key to Weight Control (or excercise in a cold room !)

Manufacturing chemicals may damage the immune system : Nature News & Comment

Diabetes Mystery: Why Are Type 1 Cases Surging?: Scientific American

Entry point for hepatitis C infection identified

High animal fat diet increases gestational diabetes risk, study finds

Genetic variation increases risk of metabolic side effects in children on some antipsychotics

High levels of fructose consumption by adolescents may put them at cardiovascular risk, evidence suggests

Food fried in olive or sunflower oil is not linked to heart disease, Spanish study finds