Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

Indexación: Web of Science; Scopus.The Human Respiratory Syncytial Virus (hRSV) is a major cause of acute lower respiratory tract infections (ARTIs) and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F), the Glycoprotein (G), and the Small Hydrophobic (SH) protein, which are located on the virus surface. In addition, the Nucleoprotein (N), Phosphoprotein (P) large polymerase protein (L) part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M) protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2). HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.https://www.frontiersin.org/articles/10.3389/fcimb.2017.00367/ful

Intestinal microbiota influences non-intestinal related autoimmune diseases

Indexación: Scopus.The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. © 2018 Opazo, Ortega-Rocha, Coronado-Arrázola, Bonifaz, Boudin, Neunlist, Bueno, Kalergis and Riedel.https://www.frontiersin.org/articles/10.3389/fmicb.2018.00432/ful

Heme oxygenase-1 as a modulator of intestinal inflammation development and progression

Indexación: Scopus.Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease. © 2018 Sebastián, Salazar, Coronado-Arrázola, Schultz, Vallejos, Berkowitz, álvarez-Lobos, Riedel, Kalergis and Bueno.https://www.frontiersin.org/articles/10.3389/fimmu.2018.01956/ful

Gestational hypothyroxinemia affects its offspring with a reduced suppressive capacity impairing the outcome of the experimental autoimmune encephalomyelitis

Indexación: Scopus.Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism. Isolated CD4+CD25+ T cells from spleen of the offspring gestated in Hpx that suffer EAE showed reduced capacity to suppress proliferation of effector T cells (TEff) after being stimulated with anti-CD3 and anti-CD28 antibodies. Moreover, adoptive transfer experiments of CD4+CD25+ T cells from the offspring gestated in Hpx suffering EAE to mice that were induced with EAE showed that the receptor mice suffer more intense EAE pathological score. Even though, no significant differences were detected in the frequency of Treg cells and IL-10 content in the blood, spleen, and brain between mice gestated in Hpx or euthyroidism, T cells CD4+CD25+ from spleen have reduced capacity to differentiate in vitro to Treg and to produce IL-10. Thus, our data support the notion that maternal Hpx can imprint the immune response of the offspring suffering EAE probably due to a reduced capacity to trigger suppression. Such "imprints" on the immune system could contribute to explaining as to why adult offspring gestated in Hpx suffer earlier and more intense EAE. © 2018 Haensgen, Albornoz, Opazo, Bugueño, Jara Fernández, Binzberger, Rivero-Castillo, Venegas Salas, Simon, Cabello-Verrugio, Elorza, Kalergis, Bueno and Riedel.https://www.frontiersin.org/articles/10.3389/fimmu.2018.01257/ful

Magnetic field diagnostics and spatio-temporal variability of the solar transition region

Magnetic field diagnostics of the transition region from the chromosphere to the corona faces us with the problem that one has to apply extreme UV spectro-polarimetry. While for coronal diagnostic techniques already exist through infrared coronagraphy above the limb and radio observations on the disk, for the transition region one has to investigate extreme UV observations. However, so far the success of such observations has been limited, but there are various projects to get spectro-polarimetric data in the extreme UV in the near future. Therefore it is timely to study the polarimetric signals we can expect for such observations through realistic forward modeling. We employ a 3D MHD forward model of the solar corona and synthesize the Stokes I and Stokes V profiles of C IV 1548 A. A signal well above 0.001 in Stokes V can be expected, even when integrating for several minutes in order to reach the required signal-to-noise ratio, despite the fact that the intensity in the model is rapidly changing (just as in observations). Often this variability of the intensity is used as an argument against transition region magnetic diagnostics which requires exposure times of minutes. However, the magnetic field is evolving much slower than the intensity, and thus when integrating in time the degree of (circular) polarization remains rather constant. Our study shows the feasibility to measure the transition region magnetic field, if a polarimetric accuracy on the order of 0.001 can be reached, which we can expect from planned instrumentation.Comment: Accepted for publication in Solar Physics (4.Mar.2013), 19 pages, 9 figure

The Oscillation Probability of GeV Solar Neutrinos of All Active Species

In this paper, I address the oscillation probability of O(GeV) neutrinos of all active flavours produced inside the Sun and detected at the Earth. Flavours other than electron-type neutrinos may be produced, for example, by the annihilation of WIMPs which may be trapped inside the Sun. In the GeV energy regime, matter effects are important both for the ``1-3'' system and the ``1-2'' system, and for different neutrino mass hierarchies. A numerical scan of the multidimensional three-flavour parameter space is performed, ``inspired'' by the current experimental situation. One important result is that, in the three-flavour oscillation case, P{alpha,beta} is different from P{beta,alpha} for a significant portion of the parameter space, even if there is no CP-violating phase in the MNS matrix. Furthermore, P{mu,mu} has a significantly different behaviour from P{tau,tau}, which may affect expectations for the number of events detected at large neutrino telescopes.Comment: 38 pages, 10 figure

Extrinsic CPT Violation in Neutrino Oscillations in Matter

We investigate matter-induced (or extrinsic) CPT violation effects in neutrino oscillations in matter. Especially, we present approximate analytical formulas for the CPT-violating probability differences for three flavor neutrino oscillations in matter with an arbitrary matter density profile. Note that we assume that the CPT invariance theorem holds, which means that the CPT violation effects arise entirely because of the presence of matter. As special cases of matter density profiles, we consider constant and step-function matter density profiles, which are relevant for neutrino oscillation physics in accelerator and reactor long baseline experiments as well as neutrino factories. Finally, the implications of extrinsic CPT violation on neutrino oscillations in matter for several past, present, and future long baseline experiments are estimated.Comment: 47 pages, 7 figures, RevTeX4. Final version to be published in Phys. Rev.

MIP-based protein profiling: A method for interspecies discrimination

Due to recent public concern and interest in the authenticity and origin of meat, for example, the 2013 “horsemeat scandal” in the human food chain, novel sensor strategies for the discrimination between protein species are highly sought after. In this work, molecularly imprinted polymers (MIPs) are utilised for protein discrimination using electrochemical sensor and spectrophotometric techniques. MIP selectivity between two proteins of similar molecular weight (haemoglobin and serum albumin) were compared across three different species, namely pork, beef and human. Bulk MIPs resulted in Kd and Bmax values of 184±23 µM, and 582 µmol g-1 for BHb, 246.3±26 µM, and 673 µmol g-1 for HHb; 276±31 µM, and 467 µmol g-1 for PHb. With the aid of chemometrics, i.e. multivariate analysis and pattern recognition, distinctive protein profiles have been achieved for species discrimination in both spectrophotometric and electrochemical analysis experiments. MIP suitability and selectivity within complex matrices was also assessed using urine, human plasma and human serum. Pattern recognition MIP-based protein profiling demonstrated positive outputs yielding either a ‘bovine’ or ‘not-bovine’ outcome (p = 0.0005) for biological samples spiked with/without bovine using respective bovine haemoglobin MIPs