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Background: Environmental modification of genetic information (epigenetics) is often invoked to explain interindividual differences in the phenotype of schizophrenia. In clinical practice, such variability is most prominent in the symptom profile and the treatment response. Epigenetic regulation of immune function is of particular interest, given the therapeutic relevance of this mechanism in schizophrenia. Methods: We analyzed the DNA methylation data of immune-relevant genes in patients with schizophrenia whose disease duration was less than 3 years, with previous lifetime antipsychotic treatment of no more than 2 weeks total. Results: A total of 441 patients met the inclusion criteria. Core symptoms were consistently associated with 206 methylation positions, many of which had previously been implicated in inflammatory responses. Of these, 24 methylation positions were located either in regulatory regions or near the CpG islands of 20 genes, including the SRC gene, which is a key player in glutamatergic signalling. These symptom-associated immune genes were enriched in neuronal development functions, such as neuronal migration and glutamatergic synapse. Compared with using only clinical information (including scores on the Positive and Negative Syndrome Scale), integrating methylation data into the model significantly improved the predictive ability (as indicated by area under the curve) for response to 8 weeks of antipsychotic treatment. Limitations: We focused on a small number of methylation probes (immune-centred search) and lacked nutritional data and direct brain-based measures. Conclusion: Epigenetic modifications of the immune system are associated with symptom severity at onset and subsequent treatment response in schizophrenia., Introduction Schizophrenia is characterized by its heterogeneity in both clinical symptoms and treatment response. It affects 24 million individuals around the world, resulting in substantially reduced life expectancy and a [...]

Background: Psoriasis (PS), vitiligo (VT), and Pityriasis rosea (PR) are chronic skin diseases often occurring as a consequence of exaggerated immune responses. These skin manifestations can be triggered as a result of the molecular mimicry between viral protein (s) and host protein (s), which could generate auto-antibodies. In addition, it can be hypothesised that skin diseases are manifestations of the reduced immunity that is observed in chronic hepatitis B virus (HBV)-infected individuals. Aims and Objective: To investigate the presence of HBV in PS, VT, and PR cases and Human Herpes Virus (HHV) 6 and 7 in PR cases. Materials and Methods: DNA extracted from healthy controls (n = 20), PS (n = 10), VT (n = 11), and PR (n = 12) were subjected to HBV-S gene-specific polymerase chain reactions (PCRs) and HHV 6-UL57 and HHV7-UL10 gene-specific PCRs. PCR products of positive samples (HBV and HHV 6 and 7 DNA) of expected length were bi-directionally sequenced using overlapping primers. Sequence identification was performed by NCBI BLAST and analysed by multiple sequence alignment. HBV DNA copy number was determined through quantitative real-time PCR. The blood samples were also tested for HBV serological markers and Interferon gamma (IFN-γ) by enzyme immunoassays. Results: The PCR data and Immunoassay study revealed that seven out of 12 PR, six out of 10 PS, and six out of 11 VT cases had signs of HBV infection. HHV 6 DNA was detected in four, whereas HHV 7 DNA was found in two of the 12 PR blood samples. PR6 presented the evidence of both HHV 6 and 7 co-infections. Conclusion: Observing the correlation of HBV with skin diseases, albeit at the pilot level, a larger study is warranted to identify HBV infection in skin disease patients. The evidence of HHV 6 and HHV 7 DNA in PR cases supports the HHV infection linkage with PR. Keywords: Co-infection, Pityriasis rosea, psoriasis, vitiligo, KEY MESSAGES: Underlying viral infections may be linked to chronic skin disease manifestations. Evidence of high frequency of HBV infection in PS, VT, and PR cases and the presence of HHV 6 and/or 7 infections in PR draw a diagnostic perspective for screening these subjects for these viruses as well., Author(s): Ruchi Supekar [1,2]; Subrata Roy [2]; Abhishek De [3]; Subhajit Biswas (corresponding author) [1,2] Introduction Psoriasis (PS), vitiligo (VT), and Pityriasis rosea (PR) are chronic skin diseases that often [...]

Background High-altitude exposure can cause oxidative stress damage in the intestine, which leads to increased intestinal permeability and bacterial translocation, resulting in local and systemic inflammation. Control of infection is critically dependent on the host's ability to kill pathogens with reactive oxygen species (ROS). Myeloperoxidase (MPO) targets ROS in pathogens. This study aimed to investigate the effects of hypoxia on the colonic mucosal barrier and myeloperoxidase (MPO)-mediated innate immune response in the colon. Methods and Results Genetically engineered mice were exposed to a hypobaric oxygen chamber for 3 days and an inflammation model was established using Salmonella Typhimurium infection. We found that hypoxic exposure caused the development of exacerbated bacterial colitis and enhanced bacterial dissemination in MPO-deficient mice. Infection and disease severity were associated with significantly increased Ly6G.sup.+ neutrophil and F4/80.sup.+ macrophage counts in infected tissues, which is consistent with elevated proinflammatory cytokines and chemoattractant molecules. Hypoxia restrained antioxidant ability and MPO deficiency aggravated the respiratory burst in the colon. Conclusion Hypoxia can damage the colonic mucosa. MPO mediates the innate immune response and regulates the mucosal and systemic inflammatory responses to Salmonella infection during hypoxia. Keywords: Hypoxia, Myeloperoxidase, Intestinal mucosa, Oxidative stress, Inflammation, Salmonella Typhimurium, Author(s): Qinfang Zhu[sup.1], Ying Han[sup.1], Xiaozhou Wang[sup.1], Ruhan Jia[sup.1], Jingxuan Zhang[sup.1], Meiheng Liu[sup.1] and Wei Zhang[sup.1] Background Gastrointestinal (GI) problems are common at high altitudes, and diarrhea is frequently observed, [...]

Byline: Jian. Han, Liting. Yang, Zhuocong. Lou, Yubo. Zhu Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRS) are being increasingly used to predict outcomes of various diseases. However, [...]

Vaccine is the most effective way to prevent the spread of communicable diseases, but the immune response induced by it varies greatly between individuals and populations in different regions of the world. Current studies have identified the composition and function of the gut microbiota as key factors in modulating the immune response to vaccination. This article mainly reviews the differences in gut microbiota among different groups of vaccinated people and animals, explores the possible mechanism of vaccine immunity affected by gut microbiota, and reviews the strategies for targeting gut microbiota to improve vaccine efficacy. Keywords: Gut microbiota, Vaccine, Immune efficacy, Author(s): Biqing Huang[sup.1,2,3], Jianwei Wang[sup.1,3] and Lanjuan Li[sup.1] Introduction Vaccine is the most effective measure to prevent communicable diseases, which could significantly reduce the morbidity, severity, and mortality of diseases, [...]

Introduction Ebola virus infection causes a rapid-onset severe acute hemorrhagic fever (Ebola virus disease, EVD) with mortality ranging from 25% to 90% depending on the outbreak (1). Clinical development of [...], BACKGROUND. NK cells are activated by innate cytokines and viral ligands to kill virus-infected cells. These functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined. METHODS. The novel 2-dose heterologous Adenovirus type 26.ZEBOV (Ad26.ZEBOV) and modified vaccinia Ankara-BN-Filo (MVA-BN-Filo) vaccine regimen is safe and provides specific immunity against Ebola glycoprotein, and is currently in phase 2 and 3 studies. Here, we analyzed NK cell phenotype and function in response to Ad26.ZEBOV, MVA-BN-Filo vaccination regimen and in response to in vitro Ebola glycoprotein stimulation of PBMCs isolated before and after vaccination. RESULTS. We show enhanced NK cell proliferation and activation after vaccination compared with baseline. Ebola glycoprotein-induced activation of NK cells was dependent on accessory cells and TLR-4-dependent innate cytokine secretion (predominantly from [CD14.sup.+] monocytes) and enriched within less differentiated NK cell subsets. Optimal NK cell responses were dependent on IL-18 and IL-12, whereas IFN-[gamma] secretion was restricted by high concentrations of IL-10. CONCLUSION. This study demonstrates the induction of NK cell effector functions early after Ad26.ZEBOV, MVA-BN-Filo vaccination and provides a mechanism for the activation and regulation of NK cells by Ebola glycoprotein. TRIAL REGISTRATION. ClinicalTrials.gov NCT02313077. FUNDING. United Kingdom Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (grant 115861) and Crucell Holland (now Janssen Vaccines and Prevention B.V.), European Union's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA).

Introduction The Himalayan marmot (Marmota himalayana) is a marmot species that inhabits alpine grasslands throughout the Himalayan regions and on the Tibetan Plateau (Nikol'skii and Ulka 2006; Hoffmann et al. [...], The Himalayan marmot (Marmota himalayana), a natural host and transmitter of plague, is also susceptible to the hepadnavirus infection. To reveal the genetic basis of the hepadnavirus susceptibility and the immune response to plague, we systematically characterized the features of immune genes in Himalayan marmot with those of human and mouse. We found that the entire major histocompatibility complex region and the hepatitis B virus pathway genes of the Himalayan marmot were conserved with those of humans. A Trim (tripartite motif) gene cluster involved in immune response and antiviral activity displays dynamic evolution, which is reflected by the duplication of Trim5 and the absence of Trim22 and Trim34. Three key regions of Ntcp, which is critical for hepatitis B virus entry, had high identity among seven species of Marmota. Moreover, we observed a severe alveolar hemorrhage, inflammatory infiltrate in the infected lungs and livers from Himalayan marmots after infection of EV76, a live attenuated Yersinia pestis strain. Lots of immune genes were remarkably up-regulated, which several hub genes H2r[gamma], Tra29, and Nlrp7 are placed at the center of the gene network. These findings suggest that Himalayan marmot is a potential animal model for study on the hepadnavirus and plague infection. Key words: Himalayan marmot, immune system, hepadnavirus, plague. La marmotte de l'Himalaya (Marmota himalayana), un hote naturel qui peut transmettre la peste, est egalement sensible a l'infection par l'hepadnavirus. Afin de reveler l'assise genetique de la sensibilite a l'hepadnavirus et de la reponse immunitaire a la peste, les auteurs ont systematiquement caracterise les genes du systeme immunitaire chez la marmotte de l'Himalaya avec ceux chez l'humain et la souris. Les auteurs ont trouve que la region entiere du complexe majeur d'histocompatibilite et les genes du sentier du virus de l'hepatite B chez la marmotte de l'Himalaya sont conserves avec ceux presents chez l'humain. Un groupe de genes Trim (<< a motif tripartite >>) implique dans la reponse immunitaire et l'activite antivirale presentait une evolution dynamique, laquelle se reflete par la duplication de Trim5 et l'absence des genes Trim22 et Trim34. Trois regions cles de Ntcp, lequel est critique pour l'entree du virus de l'hepatite B, presentaient un fort niveau d'identite au sein de sept especes de Marmota. De plus, les auteurs ont observe une severe hemorragie alveolaire, un infiltrat inflammatoire dans les poumons et le foie chez des marmottes de l'Himalaya apres infection avec l'EV76, une souche vivante attenuee du Yersinia pestis. Plusieurs genes du systeme immunitaire etaient remarquablement plus fortement exprimes, dont plusieurs genes (H2r[gamma], Tra29 et Nlrp7) qui sont au coeur de reseaux de genes. Ces observations suggerent que la marmotte de l'Himalaya constitue une espece modele potentielle pour l'etude de l'infection avec l'hepadnavirus et la peste. [Traduit par la Redaction] Mots-cles : marmotte de l'Himalaya, systeme immunitaire, hepadnavirus, peste.

Introduction Helminth parasites are well known for their capacity to modulate the parasite-directed host immune response (1, 2); with long-standing infection these parasites modulate the host response to bystander antigens/pathogens [...], This study investigates the relationship between helminth infection and allergic sensitization by assessing the influence of preexisting allergy on the outcome of helminth infections, rather than the more traditional approach in which the helminth infection precedes the onset of allergy. Here we used a murine model of house dust mite-induced (HDM-induced) allergic inflammation followed by Ascaris infection to demonstrate that allergic sensitization drives an eosinophil-rich pulmonary type 2 immune response (Th2 cells, M2 macrophages, type 2 innate lymphoid cells, IL-33, IL-4, IL-13, and mucus) that directly hinders larval development and reduces markedly the parasite burden in the lungs. This effect is dependent on the presence of eosinophils, as eosinophil-deficient mice were unable to limit parasite development or numbers. In vivo administration of neutralizing antibodies against CD4 prior to HDM sensitization significantly reduced eosinophils in the lungs, resulting in the reversal of the HDM-induced Ascaris larval killing. Our data suggest that HDM allergic sensitization drives a response that mimics a primary Ascaris infection, such that [CD4.sup.+] Th2-mediated eosinophil-dependent helminth larval killing in the lung tissue occurs. This study provides insight into the mechanisms underlying tissue-specific responses that drive a protective response against the early stages of the helminths prior to their establishing long-lasting infections in the host.

Enterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials. Keywords: Enterococcus faecium, Penicillin-binding protein, Vaccine, Epitope, Immunoinformatics, Author(s): Jyotirmayee Dey[sup.1], Soumya Ranjan Mahapatra[sup.1], T. Kiran Raj[sup.2], Taranjeet Kaur[sup.3], Parul Jain[sup.1], Arushi Tiwari[sup.1], Shubhransu Patro[sup.4], Namrata Misra[sup.1,5] and Mrutyunjay Suar[sup.1,5] Introduction Enterococcus faecium is among the most frequent [...]

Introduction Adoptive T cell therapy with receptor-modified T cells is emerging as a promising strategy to treat cancers (1). T cells are, however, not only capable of killing cancer cells, [...], Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice. We assessed virological and gene-expression changes using quantitative reverse -transcriptase PCR (qRT-PCR), immunofluorescence, and Luminex technology. HBV-specific T cells lysed HBV-producing hepatoma cells in vitro. In vivo, 3 injections of HBV-specific T cells caused progressive viremia reduction within 12 days of treatment in animals reconstituted with haplotype-matched hepatocytes, whereas viremia remained stable in mice receiving irrelevant T cells redirected toward hepatitis C virus-specific TCRs. Notably, increases in alanine aminotransferase levels, apoptotic markers, and human inflammatory cytokines returned to pretreatment levels within 9 days after the last injection. T cell transfer did not trigger inflammation in uninfected mice. These data support the feasibility of using mRNA electroporation to engineer HBV TCR-redirected T cells in patients with chronic HBV infection.

Author(s): Jyoti Chhibber-Goel[sup.1], Sreehari Gopinathan[sup.1] and Amit Sharma[sup.1] Background COVID-19 has been spreading all across the globe causing serious health concerns. COVID-19 patients have an altered gut microbiome. A proximal [...], COVID-19 is an acute respiratory distress syndrome and is often accompanied by gastrointestinal symptoms. The SARS-CoV-2 has been traced not only in nasopharyngeal and mid-nasal swabs but also in stool and rectal swabs of COVID-19 patients. The gut microbiota is important for an effective immune response as it ensures that unfavorable immune reactions in lungs and other vital organs are regulated. The human gut-lung microbiota interplay provides a framework for therapies in the treatment and management of several pulmonary diseases and infections. Here, we have collated data from COVID-19 studies, which suggest that bacterial co-infections as well as the gut-lung cross talk may be important players in COVID-19 disease prognosis. Our analyses suggests a role of gut microbiome in pathogen infections as well as in an array of excessive immune reactions during and post COVID-19 infection recovery period. Keywords: Angiotensin-converting enzyme 2, Gut-lung axis, Gut-microbiome, Opportunistic pathogens, Probiotics, SARS-CoV-2

Author(s): Jon Hazeldine 1,2,*, David N. Naumann 2, Emma Toman 2, David Davies 2, Jonathan R. B. Bishop 2, Zhangjie Su 2, Peter Hampson 1,3, Robert J. Dinsdale 1,3, Nicholas [...], Background Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS). Methods and findings The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18-90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9-66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17-60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16.sup.BRIGHT CD62L.sup.DIM neutrophils (82.07 x 10.sup.6 /l ± 18.94 control versus 1,092 x 10.sup.6 /l ± 165 trauma, p < 0.0005) and CD14.sup.+ HLA-DR.sup.low/- monocytes (34.96 x 10.sup.6 /l ± 4.48 control versus 95.72 x 10.sup.6 /l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function. Conclusions Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.