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Taken together, our findings suggest a novel mechanism by which HBsAg interacts with TAK1-TAB2 complex and suppresses the activation of NF-κB signaling pathway via reduction of the post-translational modifications and autophagic degradation.Atopic diseases in childhood are a major burden worldwide and there is still a lack of knowledge about treatable causes. In industrialized countries such as Germany, almost every second child is sensitized to at least one common allergen. Recent studies show that although the predisposition to allergies is inherited, the adaptive immune system of neonates and infants follows a developmental trajectory and whether an allergy actually occurs depends also on timing of allergen exposure including diet as well as environmental factors. New recommendations are far from being rigid of allergen avoidance; it is rather moving toward conditions that stand for more biodiversity. The observation that introduction of peanuts or eggs early in life significantly reduced the development of a later allergy will change our recommendations for the introduction of complementary foods. This is consistent with the hygiene hypothesis that early provocation shapes the developing immune system so that it reacts appropriately. Therefore, promoting the development of tolerance is at the heart of sensible allergy prevention - and this begins with the last trimester of pregnancy. In light of this concept, actual recommendations are discussed.Typically occurring during secondary dengue virus (DENV) infections, dengue hemorrhagic fever (DHF) causes abnormal immune responses, as well as endothelial vascular dysfunction, for which the responsible viral factor remains unclear. During peak viremia, the plasma levels of virion-associated envelope protein domain III (EIII) increases to a point at which cell death is sufficiently induced in megakaryocytes in vitro. Thus, EIII may constitute a virulence factor for endothelial damage. In this study, we examined endothelial cell death induced by treatment with DENV and EIII in vitro. Notably, pyroptosis, the major type of endothelial cell death observed, was attenuated through treatment with Nlrp3 inflammasome inhibitors. EIII injection effectively induced endothelial abnormalities, and sequential injection of EIII and DENV-NS1 autoantibodies induced further vascular damage, liver dysfunction, thrombocytopenia, and hemorrhage, which are typical manifestations in DHF. Under the same treatments, pathophysiological changes in the Nlrp3 inflammasome-deficient mice were notably reduced compared with those in the wild-type mice. These results suggest that the Nlrp3 inflammasome constitutes a potential therapeutic target for treating DENV-induced hemorrhage in DHF.Babesia microti is a protozoan that infects red blood cells. Babesiosis is becoming a new global threat impacting human health. Rhoptry neck proteins (RONs) are proteins located at the neck of the rhoptry and studies indicate that these proteins play an important role in the process of red blood cell invasion. In the present study, we report on the bioinformatic analysis, cloning, and recombinant gene expression of two truncated rhoptry neck proteins 2 (BmRON2), as well as their potential for incorporation in a candidate vaccine for babesiosis. Western blot and immunofluorescence antibody (IFA) assays were performed to detect the presence of specific antibodies against BmRON2 in infected mice and the localization of N-BmRON2 in B. microti parasites. In vitro experiments were carried out to investigate the role of BmRON2 proteins during the B. microti invasion process and in vivo experiments to investigate immunoprotection. Homologous sequence alignment and molecular phylogenetic analysis indicated that BmRON2cate that truncated rhoptry neck protein 2, especially its N-terminal fragment (rN-BmRON2), plays an important role in the invasion of host red blood cells, confers immune protection, and shows good potential as a candidate vaccine against babesiosis.Dyslipidemia promotes development of the atherosclerotic plaques that characterise cardiovascular disease. Plaque progression requires the influx of monocytes into the vessel wall, but whether dyslipidemia is associated with an increased potential of monocytes to extravasate is largely unknown. Here (using flow cytometry) we examined recruitment marker expression on monocytes from generally healthy individuals who differed in lipid profile. Comparisons were made between monocyte subsets, participants and relative to participants' lipid levels. Monocyte subsets differed significantly in their expression of recruitment markers, with highest expression being on either the classical or non-classical subsets. However, these inter-subset differences were largely overshadowed by considerable inter-participant differences with some participants having higher levels of recruitment markers on all three monocyte subsets. Furthermore, when the expression of one recruitment marker was high, so too was that of most of the other markers, with substantial correlations evident between the markers. The inter-participant differences were explained by lipid levels. Most notably, there was a significant inverse correlation for most markers with ApoA1 levels. Our results indicate that dyslipidemia, in particular low levels of ApoA1, is associated with an increased potential of all monocyte subsets to extravasate, and to do so using a wider repertoire of recruitment markers than currently appreciated.Since the first reported spontaneous regression of tumors in patients with streptococcus infection, cancer biological therapy was born and it evolved into today's immunotherapy over the last century. Although the original strategy was unable to impart maximal therapeutic benefit at the beginning, it laid the foundations for the development of immune checkpoint blockade and CAR-T which are currently used for cancer treatment in the clinics. However, clinical applications have shown that current cancer immunotherapy can cause a series of adverse reactions and are captious for patients with preexisting autoimmune disorders. Salmonellae was first reported to exert antitumor effect in 1935. Until now, numerous studies have proved its potency as an antitumor agent in the near future. In this review, we summarize the currently available data on the antitumor effects of Salmonella, and discussed a possibility of integrating Salmonella into cancer immunotherapy to overcome current obstacles.

Neutrophils contribute to host defense through different mechanisms, including the formation of neutrophil extracellular traps (NETs). The genetic background and underlying mechanisms contributing to NET formation remain unclear.

We performed a genome-wide association study (GWAS) and exome-sequencing analysis to identify common and rare genetic variants associated with plasma myeloperoxidase (MPO)-DNA complex levels, a biomarker for NETs, in the population-based Rotterdam Study cohort. GWAS was performed using haplotype reference consortium(HRC)-imputed genotypes of common variants in 3,514 individuals from the first and 2,076 individuals from the second cohort of the Rotterdam Study. We additionally performed exome-sequencing analysis in 960 individuals to investigate rare variants in candidate genes.

The GWAS yielded suggestive associations (p-value < 5.0 × 10

) of SNPs annotated to four genes. In the exome-sequencing analysis, a variant in

gene was significantly associated with MPO-DNA complen experimental studies.Helminth infections and their components have been shown to have the potential to modulate and attenuate immune responses. The objective of this study was to evaluate the potential protective effects of Clonorchis sinensis-derived protein (CSp) on ankylosing spondylitis (AS). Cytotoxicity of CSp at different doses was assessed by MTS and flow cytometry before performing experiments. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analyzed using flow cytometry. The levels of INF- γ , IL-17A, TNF-α, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). SKG mice were treated with CSp or vehicles. Inflammation and new bone formation were evaluated using immunohistochemistry, positron emission tomography (PET), and micro-computed tomography (CT). Treatment with CSp resulted in no reduced cell viability of PBMCs or SFMCs until 24 h. In experiments culturing PBMCs and SFMCs, the frequencies of IFN- γ and IL-17A producing cells were significantly reduced after CSp treatment. In the SKG mouse model, CSp treatment significantly suppressed arthritis, enthesitis, and enteritis. Micro-CT analysis of hind paw revealed reduced new bone formation in CSp-treated mice than in vehicle-treated mice. We provide the first evidence demonstrating that CSp can ameliorate clinical signs and cytokine derangements in AS. In addition, such CSp treatment could reduce the new bone formation of AS.Oncolytic viruses are of growing importance in cancer therapeutics since they combine direct oncolytic effect and the stimulation of antitumor immunity. Emerging evidences showed that the function of oncolytic viruses is dependent on immune response in tumor microenvironment, and the modulation of immunity could influence their efficacy. Here we combined the interleukin 10 (IL-10) and oncolytic adenovirus Ad-hTERT to treat lung cancer and explored the underlying mechanism under combination therapy. Transferase inhibitor Lewis lung carcinoma (LLC) and B16F10 tumor-bearing immunocompetent C57BL/6 mice that received Ad-hTERT or IL-10 alone showed mild antitumor effect, while the combination therapy shrink tumor bulks and prolonged survival remarkably. In addition, IL-10 didn't show direct influence on tumor cell viability or Ad-hTERT mediated tumor cell lysis in vitro. To further explore the influence of combination therapy mediated antitumor capacity, we eliminated CD8+ T, CD4+ T or natural killer (NK) cells in LLC and B16F10-bearing C57BL/6 mice, and found that CD8+ T cells were critical mediator in the combination therapy. The combination therapy induced intensive infiltration of CD8+ T cells in tumors, increased tumor-specific IFN-γ secretion by CD8+ T cells. The long-term tumor-specific immune memory induced by the combination therapy rejected rechallenge by respective tumor cell lines. This study demonstrated that the therapy combining IL-10 and Ad-hTERT augmented antitumor efficacy which was CD8+ T cells dependent. Our findings paved the way to combine cytokines and oncolytic viruses to enhance antitumor immunotherapy in treating cancer.

sensu lato (sl) is the causative agent of Lyme borreliosis. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines. DNA tattoo vaccination with

strain PKo OspC in mice has proven to be fully protective against

syringe challenge and induces a favorable humoral immunity compared to recombinant protein vaccination. Alternatively, several recombinant protein vaccines based on tick proteins have shown promising effect in tick-bite infection models. In this study, we evaluated the efficacy of DNA vaccines against

OspC or tick antigens in a tick-bite infection model.

We vaccinated C3H/HeN mice with OspC using a codon-optimized DNA vaccine or with recombinant protein. We challenged these mice with

sensu stricto (ss)-infected

nymphs. Subsequently, we vaccinated C3H/HeN mice with DNA vaccines coding for tick proteins for which recombinant protein vaccines have previously resulted in interference with tick feeding and/or

transmission Salp15, tHRF, TSLPI, and Tix-5.