Olesenrye2380

As there are no DETCs in human epidermis but only human epidermis γδ T cells, we need to understand the anti-tumor pathways used by DETCs to find analogous immune pathways in human skin, which could be exploited for novel therapeutics.Ostreid herpesvirus-1 microvariant (OsHV-1 μVar) is considered a major infectious microbe that can reduce the survival of natural or cultured oysters in summer. Because they lack an adaptive immune system, oysters are dependent on their innate immune systems to fight pathogens. The duplication and functional divergence of innate immune genes in the oyster have been studied, but the contribution of molecular mechanisms underlying innate immunity remains to be defined. Here, we identified the interacting proteins associated with Crassostrea gigas Toll-like receptors (CgTLR) using a yeast two-hybrid (Y2H) screening system. A total of eight proteins were identified that could interact with CgTLR. Three of these appeared at least four times in the screening and were related to MyD88. Two genes encoding these MyD88-like proteins, CgMyD88-1 and CgMyD88-2, possessed typical death and TIR domains. The third gene encoding an MyD88-like protein possessed only a TIR domain, and we named it CgMyD88s. CgMyD88s interacted only with CgTLR, but not CgMyD88-1 or CgMyD88-2. Both CgMyD88-1 and CgMyD88-2 mRNAs were upregulated after OsHV-1 μVar infection, whereas the expression of CgMyD88s decreased. When overexpressed in HEK293T cells, CgMyD88-1 and CgMyD88-2 activated an NF-κB reporter, whereas CgMyD88s impaired activation induced by CgMyD88-1 or CgMyD88-2. Intriguingly, the silencing of CgMyD88s using double-stranded RNA (dsRNA)-mediated RNA interference increased the expression of CgMyD88-1 and CgMyD88-2. Taken together, our results revealed that CgMyD88-1, CgMyD88-2, and CgMyD88s may all participate in the TLR-mediated innate immune pathway and that CgMyD88s served as a plug to avoid oysters from excessive inflammatory response during OsHV-1 μVar infections.Components of Mycobacterium tuberculosis (Mtb) envelope such as lipoproteins, lypoglycans, lipids, and glycolipids act as Pathogen Associated Molecular Patterns and/or antigens, hence contributing in different ways to the bacillus recognition, phagocytosis, and to immune responses modulation. However, Mtb envelope components are not only encountered at the bacillus-host direct contact but can act remotely from the bacillus envelope. Indeed, they are also released from the bacillus envelope and are detected in different compartments such as the infected cells endosomal compartments or in extracellular vesicles produced by the bacillus itself or by infected cells. Characterizing their trafficking is of main importance for our understanding of their role in host-pathogen interactions and consequently for their potential use as vaccine components. This review aims at providing an overview of the current knowledge of the nature of Mtb envelope components shuttled within extracellular vesicles, the interaction of these vesicles with host immune cells and the remaining black holes.Toll-Like Receptor 4 (TLR4) is one of the receptors of innate immunity. It is activated by Pathogen- and Damage-Associated Molecular Patterns (PAMPs and DAMPs) and triggers pro-inflammatory responses that belong to the repertoire of innate immune responses, consequently protecting against infectious challenges and boosting adaptive immunity. Mild TLR4 stimulation by non-toxic molecules resembling its natural agonist (lipid A) provided efficient vaccine adjuvants. The non-toxic TLR4 agonist monophosphoryl lipid A (MPLA) has been approved for clinical use. This suggests the development of other TLR4 agonists as adjuvants or drugs for cancer immunotherapy. TLR4 excessive activation by a Gram-negative bacteria lipopolysaccharide (LPS) leads to sepsis, while TLR4 stimulation by DAMPs is a common mechanism in several inflammatory and autoimmune diseases. TLR4 inhibition by small molecules and antibodies could therefore provide access to innovative therapeutics targeting sepsis as well as acute and chronic inflammatts or antagonists such as MPLA or Eritoran are under study for repositioning in different pharmacological contexts. The mechanism of action of the molecules and the level of TLR4 involvement in their biological activity are critically discussed.During the last decade, Salmonella enterica subspecies enterica serovar Infantis (S. Infantis) has become more prevalent across Europe with an increased capability to persist in broiler farms. In this study, we aimed to identify potential genetic causes for the increased emergence and longer persistence of S. Infantis in German poultry farms by high-throughput-sequencing. Broiler derived S. Infantis strains from two decades, the 1990s (n = 12) and the 2010s (n = 18), were examined phenotypically and genotypically to detect potential differences responsible for increased prevalence and persistence. S. Infantis organisms were characterized by serotyping and determining antimicrobial susceptibility using the microdilution method. Genotypic characteristics were analyzed by whole genome sequencing (WGS) to detect antimicrobial resistance and virulence genes as well as plasmids. To detect possible clonal relatedness within S. Infantis organisms, 17 accessible genomes from previous studies about emergent S. Infantis283 (n = 13) and ST32 (n = 2). The sensitive strains from the 1990s, belong to sequence type ST32 (n = 10) and ST1032 (n = 2). Therefore, this study confirms the emergence of a MDR S. Infantis pESI-like clone of ST2283 in German broiler farms with presumably high tendency of dissemination. Further studies on the epidemiology and control of S. Infantis in broilers are needed to prevent the transfer from poultry into the human food chain.The novel coronavirus, SARS-CoV-2, or 2019-nCoV, which originated in Wuhan, Hubei province, China in December 2019, is a grave threat to public health worldwide. A total of 3,672,238 confirmed cases of coronavirus disease 2019 (COVID-19) and 254,045 deaths were reported globally up to May 7, 2020. However, approved antiviral agents for the treatment of patients with COVID-19 remain unavailable. Drug repurposing of approved antivirals against other viruses such as HIV or Ebola virus is one of the most practical strategies to develop effective antiviral agents against SARS-CoV-2. A combination of repurposed drugs can improve the efficacy of treatment, and structure-based drug design can be employed to specifically target SARS-CoV-2. This review discusses therapeutic strategies using promising antiviral agents against SARS-CoV-2. In addition, structural characterization of potentially therapeutic viral or host cellular targets associated with COVID-19 have been discussed to refine structure-based drug design strategies.In humans, respiratory infections with influenza A viruses can be lethal, but it is unclear whether non-respiratory influenza A infections can be equally lethal. Intraperitoneal infection makes the abdominal and pelvic organs accessible to pathogens because of the circulation of peritoneal fluid throughout the pelvis and abdomen. We found that high-dose intraperitoneal infection in mice with influenza A viruses resulted in severe sclerosis and structural damage in the pancreas, disruption of ovarian follicles, and massive infiltration of immune cells in the uterus. The intraperitoneal infections also caused robust upregulation of proinflammatory mediators including IL-6, BLC, and MIG. In addition, low-dose intraperitoneal infection with one influenza strain provided cross-protection against subsequent intraperitoneal or intranasal challenge with another influenza strain. Our results suggest that low-dose, non-respiratory administration might provide a route for influenza vaccination. Furthermore, these results provide insight on the pathological role of influenza A viruses in high-risk patients, including women and diabetic individuals.Comprehensive transcriptome analysis was conducted to elucidate the molecular basis of the interaction between chestnut blight fungus, Cryphonectria parasitica, and single-stranded RNA (ssRNA) mycovirus Cryphonectria hypovirus 1 (CHV1), using RNA-sequencing (RNA-seq). A total of 1,023 differentially expressed genes (DEGs) were affected by CHV1 infection, of which 753 DEGs were upregulated and 270 DEGs were downregulated. Significant correlations in qRT-PCR analysis of 20 randomly selected DEGs and agreement with previously characterized marker genes validated our RNA-seq analysis as representing global transcriptional profiling of virus-free and -infected isogenic strains of C. parasitica. Gene Ontology (GO) analysis of DEGs indicated that "cellular aromatic compound metabolic process" and "transport" were the two most enriched components in the "biological process." In addition, "cytoplasm" was the most enriched term in the "cellular component" and "nucleotide binding" and "cation binding" were the two most enriched terms in the "molecular function" category. These results suggested that altered expression of genes encoding numerous intracellular proteins due to hypoviral infection resulted in changes in specific metabolic processes as well as transport processes. Kyoto Encyclopedia of Genes and Genomes function analysis demonstrated that pathways for "biosynthesis of other secondary metabolites," "amino acid metabolism," "carbohydrate metabolism," and "translation" were enriched among the DEGs in C. parasitica. These results demonstrate that hypoviral infection resulted in massive but specific changes in primary and secondary metabolism, of which antiviral fungal metabolites were highly induced. The results of this study provide further insights into the mechanism of fungal gene regulation by CHV1 at the transcriptome level.In September 2017 the Agia Zoni II sank in the Saronic Gulf, Greece, releasing approximately 500 tonnes of heavy fuel oil, contaminating the Salamina and Athens coastlines. Effects of the spill, and remediation efforts, on sediment microbial communities were quantified over the following 7 months. Five days post-spill, the concentration of measured hydrocarbons within surface sediments of contaminated beaches was 1,093-3,773 μg g-1 dry sediment (91% alkanes and 9% polycyclic aromatic hydrocarbons), but measured hydrocarbons decreased rapidly after extensive clean-up operations. Bacterial genera known to contain oil-degrading species increased in abundance, including Alcanivorax, Cycloclasticus, Oleibacter, Oleiphilus, and Thalassolituus, and the species Marinobacter hydrocarbonoclasticus from approximately 0.02 to >32% (collectively) of the total bacterial community. Abundance of genera with known hydrocarbon-degraders then decreased 1 month after clean-up. However, a legacy effect was observed within the bacterial community, whereby Alcanivorax and Cycloclasticus persisted for several months after the oil spill in formerly contaminated sites. This study is the first to evaluate the effect of the Agia Zoni II oil-spill on microbial communities in an oligotrophic sea, where in situ oil-spill studies are rare. The results aid the advancement of post-spill monitoring models, which can predict the capability of environments to naturally attenuate oil.