Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL.

The risk for non-Hodgkin lymphoma (NHL) is markedly increased in persons living with human immunodeficiency virus (HIV) infection, and remains elevated in those on anti-retroviral therapy (cART). Both the loss of immunoregulation of Epstein-Barr virus (EBV) infected cells, as well as chronic B-cell activation, are believed to contribute to the genesis of AIDS-related NHL (AIDS-NHL). However, the mechanisms that lead to AIDS-NHL have not been completely defined. A subset of B cells that is characterized by the secretion of IL10, as well as the expression of the programmed cell death ligand-1 (PD-L1/CD274), was recently described. These PD-L1+ B cells can exert regulatory function, including the dampening of T-cell activation, by interacting with the program cell death protein (PD1) on target cells. The role of PD-L1+ B cells in the development of AIDS-NHL has not been explored. We assessed B cell PD-L1 expression on B cells preceding AIDS-NHL diagnosis in a nested case-control study of HIV+ subjects who went on to develop AIDS-NHL, as well as HIV+ subjects who did not, using multi-color flow cytometry. Archival frozen viable PBMC were obtained from the UCLA Multicenter AIDS Cohort Study (MACS). It was seen that the number of CD19+CD24++CD38++and CD19+PD-L1+cells was significantly elevated in cases 1-4 years prior to AIDS-NHL diagnosis, compared to controls, raising the possibility that these cells may play a role in the etiology of AIDS-NHL. Interestingly, most PD-L1+ expression on CD19+ cells was seen on CD19+CD24++CD38++ cells. In addition, we showed that HIV can directly induce PD-L1 expression on B cells through interaction of virion-associated CD40L with CD40 on B cells

The proinflammatory cytokine interleukin 18 regulates feeding by acting on the bed nucleus of the stria terminalis

The proinflammatory cytokine IL-18 has central anorexigenic effects and was proposed to contribute to loss of appetite observed during sickness. Here we tested in the mouse the hypothesis that IL-18 can decrease food intake by acting on neurons of the bed nucleus of the stria terminalis (BST), a component of extended amygdala recently shown to influence feeding via its projections to the lateral hypothalamus (LH). We found that both subunits of the heterodimeric IL-18 receptor are highly expressed in the BST and that local injection of recombinant IL-18 (50 ng/ml) significantly reduced c-fos activation and food intake for at least 6 h. Electrophysiological experiments performed in BST brain slices demonstrated that IL-18 strongly reduces the excitatory input on BST neurons through a presynaptic mechanism. The effects of IL-18 are cell-specific and were observed in Type III but not in Type I/II neurons. Interestingly, IL-18-sensitve Type III neurons were recorded in the juxtacapsular BST, a region that contains BST-LH projecting neurons. Reducing the excitatory input on Type III GABAergic neurons, IL-18 can increase the firing of glutamatergic LH neurons through a disinhibitory mechanism. Imbalance between excitatory and inhibitory activity in the LH can induce changes in food intake. Effects of IL-18 were mediated by the IL-18R because they were absent in neurons from animals null for IL-18R\u3b1 (Il18ra-/-), which lack functional IL-18 receptors. In conclusion, our data show that IL-18 may inhibit feeding by inhibiting the activity of BST Type III GABAergic neurons

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Motivación y estimación del tiempo en el uso de herramientas internet informacionales y dialógicas

Se analiza la relación existente entre el grado de interés o motivación y estimación del tiempo (aspectos psicológicos) en la realización de tareas informacionales y dialógicas (aspectos comunicacionales) mediadas por internet en adolescentes chilenos. Se empleó una muestra estratificada de 120 estudiantes de 7 liceos de Chile con una media de edad de 15 años. Todos los participantes debían realizar de forma sucesiva dos tareas por internet: una primera tarea de comunicación vertical (búsqueda de información con el empleo del Google) y una segunda tarea de comunicación horizontal (diálogo por mensajería). Para cada una de las tareas se medía el tiempo percibido y el grado de interés. Los resultados muestran un interés significativamente mayor y un tiempo estimado significativamente menor en la tarea de comunicación horizontal. Desde aquí se pueden proyectar usos informacionales y educativos de interne

Author Correction: Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Protective effect of antigen delivery using monoolein-based liposomes in experimental hematogenously disseminated candidiasis

We evaluated the potential of a liposomal antigen delivery system (ADS) containing Candida albicans cell wall surface proteins (CWSP) in mediating protection against systemic candidiasis. Treatment of bonemarrow- derived dendritic cells with CWSP-loaded dioctadecyldimethylammonium bromide:monoolein (DODAB:MO) liposomes enhanced and prolonged their activation comparatively to free antigen, indicating that liposome-entrapped CWSP were released more sustainable. Therefore, we immunized mice with CWSP either in a free form or loaded into two different DODAB:MO liposome formulations, respectively designated as ADS1 and ADS2, prior to intravenous C. albicans infection. Immunization with ADS1, but not with ADS2, conferred significant protection to infected mice, comparatively to immunization with CWSP or empty liposomes as control. ADS1-immunized mice presented significantly higher serum levels of C. albicans-specific antibodies that enhanced phagocytosis of this fungus. In these mice, a mixed cytokine production profile was observed encompassing IFN-c, IL-4, IL-17A and IL-10. Nevertheless, only production of IL-4, IL-17 and IL-10 was higher than in controls. In this study we demonstrated that DODAB:MO liposomes enhance the immunogenicity of C. albicans antigens and host protection in a murine model of systemic candidiasis. Therefore, this liposomal adjuvant could be a promising candidate to assess in vaccination against this pathogenic fungus.This work was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI). Catarina Carneiro holds scholarship SFRH/BD/69068/2010. We acknowledge NanoDelivery-I&D em Bionanotecnologia, Lda for access to their equipment