Muscodor crispansis a recently described novel endophytic fungus ofAnanas ananassoides(wild pineapple) growing in the Bolivian Amazon Basin. The fungus produces a mixture of volatile organic compounds (VOCs); some of the major components of this mixture, as determined by GC/MS, are propanoic acid, 2-methyl-, methyl ester; propanoic acid, 2-methyl-; 1-butanol, 3-methyl-;1-butanol, 3-methyl-, acetate; propanoic acid, 2-methyl-, 2-methylbutyl ester; and ethanol. The fungus does not, however, produce naphthalene or azulene derivatives as has been observed with many other members of the genusMuscodor. The mixture of VOCs produced byM. crispanscultures possesses antibiotic properties, as does an artificial mixture of a majority of the components. The VOCs of the fungus are effective against a wide range of plant pathogens, including the fungiPythium ultimum,Phytophthora cinnamomi,Sclerotinia sclerotiorumandMycosphaerella fijiensis(the black sigatoka pathogen of bananas), and the serious bacterial pathogen of citrus,Xanthomonas axonopodispv.citri.In addition, the VOCs ofM. crispanskilled several human pathogens, includingYersinia pestis,Mycobacterium tuberculosisandStaphylococcus aureus. Artificial mixtures of the fungal VOCs were both inhibitory and lethal to a number of human and plant pathogens, including three drug-resistant strains ofMycobacterium tuberculosis.The gaseous products ofMuscodor crispanspotentially could prove to be beneficial in the fields of medicine, agriculture, and industry.

A Phoma sp. was isolated and characterized as endophytic and as a pathogen of Larrea tridentata (creosote bush) growing in the desert region of south

Background & Aims Liver sinusoidal endothelial cells (LSECs) make up a large proportion of the nonparenchymal cells in the liver. LSECs are involved in induction of immune tolerance, but little is known about their functions during hepatitis C virus (HCV) infection. Methods Primary human LSECs (HLSECs) and immortalized liver endothelial cells (TMNK-1) were exposed to various forms of HCV, including full-length transmitted/founder virus, sucrose-purified Japanese fulminant hepatitis-1 (JFH-1), a virus encoding a luciferase reporter, and the HCV-specific pathogen-associated molecular pattern molecules. Cells were analyzed by confocal immunofluorescence, immunohistochemical, and polymerase chain reaction assays. Results HLSECs internalized HCV, independent of cell–cell contacts; HCV RNA was translated but not replicated. Through pattern recognition receptors (Toll-like receptor 7 and retinoic acid–inducible gene 1), HCV RNA induced consistent and broad transcription of multiple interferons (IFNs); supernatants from primary HLSECs transfected with HCV-specific pathogen-associated molecular pattern molecules increased induction of IFNs and IFN-stimulated genes in HLSECs. Recombinant type I and type III IFNs strongly up-regulated HLSEC transcription of IFN λ3 (IFNL3) and viperin (RSAD2), which inhibit replication of HCV. Compared with CD8⁺ T cells, HLSECs suppressed HCV replication within Huh7.5.1 cells, also inducing IFN-stimulated genes in co-culture. Conditioned media from IFN-stimulated HLSECs induced expression of antiviral genes by uninfected primary human hepatocytes. Exosomes, derived from HLSECs after stimulation with either type I or type III IFNs, controlled HCV replication in a dose-dependent manner. Conclusions Cultured HLSECs produce factors that mediate immunity against HCV. HLSECs induce self-amplifying IFN-mediated responses and release of exosomes with antiviral activity.

Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3–restricted manner. Using ELISPOT analysis, a greater number of IFN-γ– and IL-2–secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.

Significance: Immune responses to modified self-proteins are involved in the pathogenesis of a number of autoimmune diseases. Type 1 diabetes (T1D) is a prototypical organ-specific autoimmune disease that results from the T-cell–mediated destruction of insulin-producing β-cells within pancreatic islets. The stages of T1D development allow for the measurement of immune responses prior to clinical symptom onset. In our study, we measured T-cell responses from genetically at-risk individuals to both naturally occurring insulin and hybrid insulin peptides, novel neo-epitopes implicated in T1D pathogenesis. Our results have important implications to stratify the risk of developing T1D and identifying individuals who may benefit from immune intervention studies.

T cells targeting self-proteins are important mediators in autoimmune diseases. T cells express unique cell-surface receptors (TCRs) that recognize peptides presented by major histocompatibility molecules. TCRs have been identified from blood and pancreatic islets of individuals with type 1 diabetes (T1D). Here, we tracked ~1700 known antigen-specific TCR sequences, islet antigen or viral reactive, in bulk TCRβ sequencing from longitudinal blood DNA samples in at-risk cases who progressed to T1D, age/sex/human leukocyte antigen–matched controls, and a new-onset T1D cohort. Shared and frequent antigen-specific TCRβ sequences were identified in all three cohorts, and viral sequences were present across all ages. Islet sequences had different patterns of accumulation based upon antigen specificity in the at-risk cases. Furthermore, 73 islet-antigen TCRβ sequences were present in higher frequencies and numbers in T1D samples relative to controls. The total number of these disease-associated TCRβ sequences inversely correlated with age at clinical diagnosis, indicating the potential to use disease-relevant TCR sequences as biomarkers in autoimmune disorders.