Drugs that suppress immune system may protect against Parkinson's: People who take immunosuppressants less likely to develop the disease -- ScienceDaily

Racette and colleagues analyzed Medicare Part D prescription drug
data on 48,295 people diagnosed with Parkinson's in 2009 and 52,324
people never diagnosed with Parkinson's. They identified 26 commonly
prescribed immunosuppressant drugs, representing six classes of
medications. The researchers determined which people in the data set had
been prescribed any of the drugs a year or more before the date of
diagnosis or by a pre-set cutoff date. Prescriptions written in the 12
months before diagnosis or by the cutoff were excluded to rule out any
chance that the prescriptions might have been linked to early signs of
the disease.
The researchers found that people taking drugs in either of two
classes were significantly less likely to develop Parkinson's than those
taking no immunosuppressants. People taking corticosteroids such as
prednisone were 20 percent less likely to be diagnosed with Parkinson's,
while those on inosine monophosphate dehydrogenase (IMDH) inhibitors
were about one-third less likely.

Here's the paper:-

Immunosuppressants and Risk of Parkinson Disease. Annals of Clinical and Translational Neurology, May 31, 2018

Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia | Translational Psychiatry

The role of the human microbiome in health and disease is increasingly
appreciated. We studied the composition of microbial communities present
in blood across 192 individuals, including healthy controls and
patients with three disorders affecting the brain: schizophrenia,
amyotrophic lateral sclerosis, and bipolar disorder. By using
high-quality unmapped RNA sequencing reads as candidate microbial reads,
we performed profiling of microbial transcripts detected in whole
blood. We were able to detect a wide range of bacterial and archaeal
phyla in blood. Interestingly, we observed an increased microbial
diversity in schizophrenia patients compared to the three other groups.
We replicated this finding in an independent schizophrenia case–control
cohort. This increased diversity is inversely correlated with estimated
cell abundance of a subpopulation of CD8⁺ memory T cells in healthy controls, supporting a link between microbial products found in blood, immunity and schizophrenia.

Monocyte activation detected prior to a diagnosis of schizophrenia in the US Military New Onset Psychosis Project (MNOPP)

 : Low-grade inflammation is present in some cases of schizophrenia, particularly in
the early stages of this disorder. The inflammation source is not known but may be
the result of dysbiotic processes occurring in the gut. We examined peripheral biomarkers
of bacterial translocation, soluble CD14 (sCD14) and lipopolysaccharide binding protein
(LBP), and of general inflammation, C-reactive protein (CRP), in a unique, pre-onset
study of schizophrenia. This sample was composed of 80 case-control matched pairs
of US military service members from whom blood samples were obtained at time of entry
to service, before a psychiatric diagnosis was made.

Immune Cells Mistake Heart Attacks for Viral Infections

 What is it about dying cells in the heart that stimulates the immune
system? To answer this, researchers looked deep inside thousands of
individual cardiac immune cells and mapped their individual
transcriptomes using a method called single cell RNA-Seq. This led to
the discovery that after a heart attack, DNA from dying cells
masquerades as a virus and activates an ancient antiviral program called
the type I interferon response in specialized immune cells. ¬¬ The
researchers named these "interferon inducible cells (IFNICs)."


When investigators blocked the interferon response, either
genetically or with a neutralizing antibody given after the heart
attack, there was less inflammation, less heart dysfunction, and
improved survival. Specifically, blocking antiviral responses in mice
improved survival from 60 percent to over 95 percent. These findings
reveal a new potential therapeutic opportunity to prevent heart attacks
from progressing to heart failure in patients.

Here's the paper:-

IRF3 and type I interferons fuel a fatal response to myocardial infarction

Confronted with bacteria, infected cells die so others can live, study finds -- ScienceDaily

 The immune system is contantly performing surveillance to detect foreign organisms that might do harm. But pathogens, for their part, have evolved a number of strategies to evade this detection, such as secreting proteins that hinder a host's ability to mount an immune response.

In a new study, a team of researchers led by Igor E. Brodsky of the University of Pennsylvania, identified a "back-up alarm" system in host cells that responds to a pathogen's attempt to subvert the immune system.

"In the context of an infection, the cells that are dying are talking to the other cells that aren't infected," said Brodsky, an assistant professor in the Department of Pathobiology in Penn's School of Veterinary Medicine and senior author on the study. "I don't think of it as altruistic, exactly, but it's a way for the cells that can't respond any longer to still alert their neighbors that a pathogen is present.""



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‘Adrenaline’ of Immune System Discovered

Scientists at the Champalimaud Centre for the Unknown and the Instituto de Medicina Molecular, in Lisbon, Portugal, have discovered that neurons located at mucosal tissues can immediately detect an infection in the organism, promptly producing a substance that acts as an “adrenaline rush” for immune cells. Under the effect of this signal, immune cells rapidly become poised to fight the infection and repair the damage caused to surrounding tissues. These totally novel results have been published online in the journal Nature on September 6, 2017.


Published in Nature:- Neuronal regulation of type 2 innate lymphoid cells via neuromedin U” by Vânia Cardoso, Julie Chesné, Hélder Ribeiro, Bethania García-Cassani, Tânia Carvalho, Tiffany Bouchery, Kathleen Shah, Nuno L. Barbosa-Morais, Nicola Harris & Henrique Veiga-Fernandes in Nature. Published online September 6 2017 doi:10.1038/nature23469

Cancer Onset May Be Caused by Immune System Fighting Viruses | GEN

 "The development of an advanced immune system to fight off microbial pathogens is a considerable part of the evolutionary success of multicellular organisms. Yet, like most success stories there is always a flip side. New evidence from investigators at the University of Colorado (CU) Cancer Center shows how the action of various immunity-based enzymes can spill over onto the host genome when trying to fight off various viral pathogens—ultimately leading to cancer-causing DNA mutations. Findings from the new study were published recently in Viruses, in an article entitled “Roles of APOBEC3A and APOBEC3B in Human Papillomavirus Infection and Disease Progression.”"

What Sensory Receptors Do Outside of Sense Organs | The Scientist Magazine®

Odor, taste, and light receptors are present in many different parts of the body, and they have surprisingly diverse functions.

Disrupted immunity in the fetal brain is linked to neurodevelopmental disorders

Disrupted fetal immune system development, such as that caused by viral infection in the mother, may be a key factor in the later appearance of certain neurodevelopmental disorders. This finding emerges from a Weizmann Institute study published in Science on June 23, 2016.
The study may explain, among other things, how the mother's infection with the cytomegalovirus (CMV) during pregnancy, which affects her own and her fetus's immune system, increases the risk that her offspring will develop autism or schizophrenia, sometimes years later. This increased risk of neurodevelopmental diseases had been discovered many years ago in epidemiological studies and confirmed in mouse models. The Weizmann study, led by Dr. Ido Amit and Prof. Michal Schwartz, of the Immunology and Neurobiology Departments, respectively, provides a possible explanation for this increase on the cellular and the mechanistic molecular levels.

Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: potential role of enhanced maternal immune activity? - PubMed - NCBI

Viral infections during the prenatal or early childhood periods are one of the environmental factors which might play an etiological role in psychoses. Several studies report higher antibody levels against viruses during pregnancy in blood of mothers of offspring with psychotic disorders, but the presence of such viruses has never been demonstrated. The goal of this study was to investigate the potential association between viral infections during pregnancy and progeny with psychotic disorders and, for this purpose, we performed a nested case-control study involving pregnant mothers of offspring with schizophrenia or bipolar disorder with psychotic features (cases, N=43) and pregnant women with healthy offspring (controls, N=95). Since several potential viral candidates have been suggested in prior work, a broad-spectrum virus detection system was necessary. A metagenomic analysis performed with the virus discovery method VIDISCA-454 revealed only common blood-associated viruses in all cohorts. However, a significantly lower viral prevalence was detected in the group of cases and in the sub-population of pregnant mothers of offspring with schizophrenia (p<0.05). Consistent with the existing inverse correlation between the level of these viruses and the immunocompetence of an individual, we hypothesized the presence of a higher immune activity during pregnancy in mothers whose offspring later develop a psychotic disorder as compared to controls. Combining our results with previously available literature data on antibody levels during the gestation period suggests that a more prominent maternal immune activity can be considered a risk factor for developing psychosis.



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Body's immune system may play larger role in Alzheimer's disease than thought - Medical News Today

Body's immune system may play larger role in Alzheimer's disease than thought - Medical News Today: "Immune cells that normally help us fight off bacterial and viral infections may play a far greater role in Alzheimer's disease than originally thought, according to University of California, Irvine neurobiologists with the Sue & Bill Gross Stem Cell Research Center and the Institute for Memory Impairments and Neurological Disorders."

The researchers discovered this when Alzheimer's disease mice genetically modified to lack these key immune cells in their blood developed the distinctive brain plaques associated with the neurodegenerative disorder much more quickly.

Schizophrenia risk from complex variation of complement component 4 : Nature :

: "Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia’s strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

"



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Schizophrenia and the Synapse | The Scientist Magazine®

Compared to the brains of healthy individuals, those of people with schizophrenia have higher expression of a gene called Complement C4, according to a paper published in Nature today (January 27). The gene encodes an immune protein that moonlights in the brain as an eradicator of unwanted neural connections (synapses). The findings, which suggest increased synaptic pruning is a feature of the disease, are a direct extension of genome-wide association studies (GWASs) that pointed to the major histocompatibility (MHC) locus as a key region associated with schizophrenia risk.

Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells. - PubMed - NCBI

The existing large-scale genome-wide association studies (GWAS) datasets provide strong support for investigating the mechanisms of Alzheimer's disease (AD) by applying multiple methods of pathway analysis. Previous studies using selected single nucleotide polymorphisms (SNPs) with several thresholds of nominal significance for pathway analysis determined that the threshold chosen for SNPs can reflect the disease model. Presumably, then, pathway analysis with a stringent threshold to define "associated" SNPs would test the hypothesis that highly associated SNPs are enriched in one or more particular pathways. Here, we selected 599 AD variants (P < 5.00E-08) to investigate the pathways in which these variants are enriched and the cell types in which these variants are active. Our results showed that AD variants are significantly enriched in pathways of the immune system. Further analysis indicated that AD variants are significantly enriched for enhancers in a number of cell types, in particular the B-lymphocyte, which is the most substantially enriched cell type. This cell type maintains its dominance among the strongest enhancers. AD SNPs also display significant enrichment for DNase in 12 cell types, among which the top 6 significant signals are from immune cell types, including 4 B cells (top 4 significant signals) and CD14+ and CD34+ cells. In summary, our results show that these AD variants with P < 5.00E-08 are significantly enriched in pathways of the immune system and active in immune cells. To a certain degree, the genetic predisposition for development of AD is rooted in the immune system, rather than in neuronal cells.

Viruses transfer the antiviral second messenger cGAMP between cells

 "Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development."

Researchers Find Missing Link Between the Brain and Immune System | Neuroscience News

In a stunning discovery that overturns decades of textbook teaching,
researchers at the University of Virginia School of Medicine have
determined that the brain is directly connected to the immune system by
vessels previously thought not to exist. That such vessels could have
escaped detection when the lymphatic system has been so thoroughly
mapped throughout the body is surprising on its own, but the true
significance of the discovery lies in the effects it could have on the
study and treatment of neurological diseases ranging from autism to
Alzheimer’s disease to multiple sclerosis.

Here's the Nature paper:-

Structural and functional features of central nervous system lymphatic vessels

One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment1, 2, 3, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood4, 5, 6. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: Potential role of enhanced maternal immune activity? - PubMed - NCBI

Viral infections during the prenatal or early childhood periods are one
of the environmental factors which might play an etiological role in
psychoses. Several studies report higher antibody levels against viruses
during pregnancy in blood of mothers of offspring with psychotic
disorders, but the presence of such viruses has never been demonstrated.
The goal of this study was to investigate the potential association
between viral infections during pregnancy and progeny with psychotic
disorders and, for this purpose, we performed a nested case-control
study involving pregnant mothers of offspring with schizophrenia or
bipolar disorder with psychotic features (cases, N=43) and pregnant
women with healthy offspring (controls, N=95). Since several potential
viral candidates have been suggested in prior work, a broad-spectrum
virus detection system was necessary. A metagenomic analysis performed
with the virus discovery method VIDISCA-454 revealed only common
blood-associated viruses in all cohorts. However, a significantly lower
viral prevalence was detected in the group of cases and in the
sub-population of pregnant mothers of offspring with schizophrenia
(p<0.05). Consistent with the existing inverse correlation between
the level of these viruses and the immunocompetence of an individual, we
hypothesized the presence of a higher immune activity during pregnancy
in mothers whose offspring later develop a psychotic disorder as
compared to controls. Combining our results with previously available
literature data on antibody levels during the gestation period suggests
that a more prominent maternal immune activity can be considered a risk
factor for developing psychosis.

Seasonal immunity: Activity of thousands of genes differs from winter to summer -- ScienceDaily

Our immune systems vary with the seasons, according to a study that
could help explain why certain conditions such as heart disease and
rheumatoid arthritis are aggravated in winter whilst people tend to be
healthier in the summer. The study shows that the activity of almost a
quarter of our genes (5,136 out of 22,822 genes tested) differs
according to the time of year, with some more active in winter and
others more active in summer. This seasonality also affects our immune
cells and the composition of our blood and adipose tissue (fat).

Scientists discover robust evidence that chronic fatigue syndrome is a biological illness

"Researchers at the Center for Infection and Immunity at Columbia University's Mailman School of Public Health identified distinct immune changes in patients diagnosed with chronic fatigue syndrome, known medically as myalgic encephalomyelitis (ME/CFS) or systemic exertion intolerance disease. The findings could help improve diagnosis and identify treatment options for the disabling disorder, in which symptoms range from extreme fatigue and difficulty concentrating to headaches and muscle pain."



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Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice.

 Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic symptoms such as hyperlocomotion, anxiolytic-like behaviors, prepulse inhibition deficits, social withdrawal, and cognitive impairments were observed in TLR-2 knock-out (KO) mice. Ventricle enlargement, a hallmark of schizophrenia, was also observed in TLR-2 KO mouse brains. Levels of p-Akt and p-GSK-3α/β were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice. Antipsychotic drugs such as haloperidol or clozapine reversed behavioral and biochemical alterations in TLR-2 KO mice. Furthermore, p-Akt and p-GSK-3α/β were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice. Thus, our data suggest that the dysregulation of the innate immune system by a TLR-2 deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling.