Consequences of Aryl hydrocarbon receptor activation in dendritic cells

TCDD (dioxin) causes immunosuppression via activation of the Aryl hydrocarbon receptor (AhR). Dendritic cells (DCs), the professional antigen-presenting cells in the immune system, are adversely affected by TCDD. However, limited information exists regarding the effects of AhR activation on DCs. We evaluated the consequences of AhR activation by TCDD on both steady-state and inflammatory DCs using in vivo and in vitro approaches, respectively. We hypothesized that AhR activation alters DC homeostasis and differentiation leading to generation of immunosuppression. C57Bl/6 mice gavaged with an immunosuppressive dose of TCDD (15 ug/kg) displayed decreased frequency and number of splenic CD11chigh DCs on day 7. Moreover, TCDD induced a selective loss of the CD11chighCD8á-33D1+ splenic DCs subset, specialized at activating CD4+ T cells, but not the regulatory CD11chighCD8á+DEC205+ splenic DCs. Additionally, TCDD increased the expression of CD86 and CD54, while decreasing the frequency of CD11a and MHC II on the splenic CD11chigh DCs. Although TCDD did not alter the number and frequency of CD11clow splenic DCs, it decreased their MHC II and CD11a expression. The loss of CD11chigh DC was independent of an apoptotic event but involved a CCR7-mediated migratory event. Popliteal and brachial lymph node (PBLNs) CD11c+ cells displayed elevated levels of MHC II and CD40, but not DC loss following TCDD exposure. To examine the effects of TCDD on inflammatory DCs, BMDCs were generated in the presence of GM-CSF and vehicle or TCDD. TCDD decreased CD11c expression but increased MHC II, CD86 and CD25 expression on these BMDCs. These effects were AhR-dependent but not exclusively DRE-mediated. Additionally, TCDD modulated antigen uptake and increased LPS- and CpG-induced IL-6 and TNF-á levels but decreased nitric oxide production by the BMDCs. TCDD downregulated LPS- and CpG-induced p65 levels and induced a trend towards upregulation of RelB levels in BMDCs. Despite the induction of suppressive mediators IDO1, IDO2 and TGFâ3, TCDD-BMDCs failed to suppress T cell activation in vivo or induce the generation of adaptive T-regs in vitro. Collectively, our data suggest that AhR activation disrupts DC homeostasis, modulates DC differentiation, TLR responsiveness and induces a regulatory phenotype, effects that may underlie TCDD-induced immunosuppression

Differential Regulation of the Immune Response in the Spleen and Liver of Mice Infected with Leishmania donovani

Immunity to pathogens requires generation of effective innate and adaptive immune responses. Leishmania donovani evades these host defense mechanisms to survive and persist in the host. A better understanding and identification of mechanisms that L. donovani employs for its survival is critical for developing novel therapeutic interventions that specifically target the parasite. This paper will highlight some of the mechanisms that the parasite utilizes for its persistence and also discuss how the immune response is regulated

Further characterization of pathogenic lung Th2 memory cells in experimental allergic asthma

Unser Labor hat bereits nachgewiesen, dass Mäuse welche sich von allergischem Asthma erholt haben, verbleibende Th2 Gedächtnis T-Zellen in der Lunge aufweisen. Da diese Th2 Zellen bei einem erneuten Auftreten der Krankheit involviert sind, war unser Ziel, die Mechanismen, die an der Erhaltung der pathogenen Th2 Zellen in der Lunge bei experimentellem allergischem Asthma beteiligt sind, besser zu charakterisieren. Eine Möglichkeit ist, dass Chemokin-Chemokinrezeptor (CKR) Interaktionen eine Rolle bei dem Überleben dieser T-Zellen spielen. Deswegen erforschten wir die Genexpression dieser Rezeptoren und deren Liganden auf Lungen-Zellen, während der Remission und einem Rückfall der Krankheit. CD4+ T-Zellen aus Lungen von genesenen Mäusen exprimieren eine breitere Palette an CKR, verglichen zu naiven Zellen. Die Expression dieser Rezeptoren war nach erneuter Antigen-Exponierung noch weiter erhöht. Um die Funktion der Gedächtnis Th2 Zellen genauer zu charakterisieren, versuchten wir diese durch Splenektomie, subletale Bestrahlung, oder durch Verabreichung von Corticosteroiden zu beseitigen. Die Corticosteroidbehandlung und eine subletale Bestrahlung konnten einen Rückfall der Krankheit nicht vollständig verhindern, wobei Splenektomie den Rückfall der Krankheit sogar verschlimmerte. Diese Daten erläutern die interessanten Eigenschaften dieser langlebenden Gedächtnis Zellen, die in den Lungen von Mäusen mit allergischem Asthma residieren. Weiters beinhaltet diese Studie wichtige klinische Implikationen, da sie Einblicke in die Mechanismen von chronischem und Steroid- resistentem allergischem Asthma gewährt. Diese Dissertation enthält Multimediabeilagen (Bilder).Our lab previously established that mice recovered from allergic asthma maintain memory Th2 cells in the lung. Since these Th2 cells are involved in the relapsing and remitting course of the disease, our aim was to further characterizes and understand the mechanisms involved in maintenance of the pathogenic lung Th2 cells in experimental allergic asthma. One possibility is that chemokine –CKR interactions play a role in the survival of T cells. We, thus, investigated the gene and cell surface protein expression of these receptors and their ligands on lung cells during remission and relapse. Recovered lung CD4+ T cells expressed a wide array of CKRs compared with naïve cells and these receptors were further elevated upon Ag rechallenge. To further characterize memory Th2 cells, we attempted to eliminate them by splenectomy, sublethal irradiation and corticosteroids. Corticosteroid and sublethal irradiation could not completely abrogate disease relapse and splenectomy actually increased disease relapse. These data further illustrate the interesting properties of long-lived memory Th2 cells that reside in the lungs of mice with allergic asthma and have important clinical implications as they may shed light on the mechanisms involved in chronic and steroid-resistant allergic asthma. The thesis inculdes Multimediabeilage (pictures

Synergistic study on electrochemically deposited thin film with a spectrum from micro to nano range structures

Thin films are deposited onto bulk materials (substrates) to achieve properties unattainable or not easily attainable in the substrates alone. The film thickness usually varies from few nanometers to a maximum value of 1 μm. Cavitation, irradiation of liquid with high intensity ultrasound, as a means of altering the crystallization process is achieved by the repeated creation and collapse of microscopic bubbles inside the solution. It is at the solid-liquid interface that electrochemical techniques may be employed to detect the possible influence of sonication on electrochemical nucleation and growth of clusters. In this work we prepare the copper thin film by sonoelectrosynthesis method at different temperature, acid and concentration of electrolyte. Films are characterized by XRD, SEM, AFM, and study of the mechanical properties is done by nanaoidentation. Scahifker and Hills model was used for study of nucleation and growth phenomena for electrochemically deposited thin film by cyclic voltammetry and chronoamperometry. A potential of 450 mV (100 mV negative than the Nernst potential) was selected for the deposition procedure for all the conditions. The sole impact of sonication was experimented before the study of the coupling effect and was found to favor nucleation ahead of growth. The evidence of secondary nucleation in ultrasonic condition was also observed. The thickness of films lies in the range of 400-500 nm. The phases of the deposits are confirmed by the XRD analysis. The nucleation population density got increased from a low value to high value of acid concentrations. Comparison with the theoretical models, it is apparent that copper follows progressive nucleation mode in increasing acid concentration. Hydrogen evolution was also imperative at increasing acid concentrations, however, ultrasound capable of degassing produced hydrogen free adherent surfaces. The facts are also confirmed by the morphological analysis by SEM and AFM. The same trend is observed for the films with low temperatures. Among all the depositions copper films at – 4 °C is the smoothest. Increasing metal ion concentrations produces finer and harder deposits. Films are rougher at 0.1 M as compared to that of 0.025 M. The grains are found to vary from 400 nm to 50 nm at various conditions with the average roughness factors from 300 nm to 14 nm

North South Asymmetry of Different Solar Activity Features During Solar Cycle 23

A study on North South (NS) asymmetry of different solar activity features (DSAF) such as solar proton events, solar active prominences, H alpha flare index, soft X ray flares, monthly mean sunspot area and monthly mean sunspot number were carried out from 1996 to 2008. It is found in our result that solar cycle 23 is magnetically weak compared to solar cycle 22. Study shows the Southern dominance of DSAF during the time period of study. During the rising phase of the cycle the numbers of DSAF approximately equal on the North and South Hemisphere. However, these activities tend to shift from Northern Hemisphere to Southern Hemisphere in between year 1998 to 1999. The statistical significance of the asymmetry time series using a chi square test of goodness of fit indicates that in most of the cases the asymmetry is highly significant, i.e., the asymmetry is a real feature in the NS distribution of DSAF.Comment: In this manuscript total 19 pages including 7 figures and 3 table

Study of Distribution and Asymmetry of Solar Active Prominences During Solar Cycle 23

In this paper we present the results of a study of the spatial distribution and asymmetry of solar active prominences (SAP) for the period 1996-2007 (solar cycle 23). For more meaningful statistical analysis we have analysed the distribution and asymmetry of SAP in two subdivisions viz. Group1 (ADF, APR, DSF, CRN, CAP) and Group2 (AFS, ASR, BSD, BSL, DSD, SPY, LPS). The north-south (N-S) latitudinal distribution shows that the SAP events are most prolific in the 21-30degree slice in the northern and southern hemispheres and east-west (E-W) longitudinal distribution study shows that the SAP events are most prolific (best visible) in the 81-90degree slice in the eastern and western hemispheres. It has been found that the SAP activity during this cycle is low compared to previous solar cycles. The present study indicates that during the rising phase of the cycle the number of SAP events were roughly equal on the north and south hemispheres. However, activity on the southern hemisphere has been dominant since 1999. Our statistical study shows that the N-S asymmetry is more significant then the E-W asymmetry.Comment: 21 pages 5 figures; Published online; 02 October, 2009; Solar Physics Journa

Protozoan Parasites and Type I IFNs

International audienceFor many years, the role of interferon (IFN)-I has been characterized primarily in the context of viral infections. However, regulatory functions mediated by IFN-I have also been described against bacterial infections and in tumor immunology. Only recently, the interest in understanding the immune functions mediated by IFN-I has dramatically increased in the field of protozoan infections. In this review, we discuss the discrete role of IFN-I in the immune response against major protozoan infections: Plasmodium, Leishmania, Trypanosoma, and Toxoplasma