Layers of dendritic cell-mediated T cell tolerance, their regulation and the prevention of autoimmunity.

The last decades of Nobel prize-honored research have unequivocally proven a key role of dendritic cells (DCs) at controlling both T cell immunity and tolerance. A tight balance between these opposing DC functions ensures immune homeostasis and host integrity. Its perturbation could explain pathological conditions such as the attack of self tissues, chronic infections, and tumor immune evasion.

Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis.

Background: Given the current lack of effective vaccines against TB, the accuracy of screening tests for determining or excluding latent TB infection (LTBI) is decisive in effective TB control. This meta-analysis critically appraises studies investigating the positive and the negative predictive value (PPV and NPV, respectively) from a test-determined LTBI state for progression to active TB of interferon-γ release assays (IGRAs) and the tuberculin skin test (TST).

Methods: We searched MEDLINE, EMBASE, and Cochrane bibliographies for relevant articles.

Inactivation and survival of hepatitis C virus on inanimate surfaces.

Background: Hepatitis C virus (HCV) cross-contamination from inanimate surfaces or objects has been implicated in transmission of HCV in health-care settings and among injection drug users. We established HCV-based carrier and drug transmission assays that simulate practical conditions to study inactivation and survival of HCV on inanimate surfaces.

Methods: Studies were performed with authentic cell culture derived viruses.

Tertiary lymphoid tissues in the colon: friend and foe.

In mammals, a variety of different lymphoid tissues have evolved as an integral part of the immune system that allows the host to survive in a sometimes hostile environment. While the development of secondary lymphoid organs is programmed in the fetus, the induction of other lymphoid structures like isolated lymphoid follicles (ILFs) in the gut or tertiary lymphoid tissues (tLT) need additional external triggers after birth. It is well established that for the development of secondary lymphoid organs, as well as ILFs, RORgt expressing lymphoid tissue inducer (LTi) cells play an important role.

CD8+ Foxp3+ T cells share developmental and phenotypic features with classical CD4+ Foxp3+ regulatory T cells but lack potent suppressive activity.

"Suppressor T cells" were historically defined within the CD8(+) T-cell compartment and recent studies have highlighted several naturally occurring CD8(+) Foxp3(-) Treg populations. However, the relevance of CD8(+) Foxp3(+) T cells, which represent a minor population in both thymi and secondary lymphoid organs of nonmanipulated mice, remains unclear. We here demonstrate that de novo Foxp3 induction in peripheral CD8(+) Foxp3(-) T cells is counter-regulated by DC-mediated co-stimulation via CD80/CD86.

A modified "far-lateral" approach for safe resection of retroodontoid dural cysts.

Cystic mass lesions at the ventral craniocervical junction have been described only rarely in the past, however, they have received more attention with improved imaging modalities in recent years. These lesions have been approached by various operative procedures. A modified "far-lateral" approach combined with a C1 hemilaminectomy without fusion was used to safely remove the cyst and decompress the cervical medulla in a 72-year-old woman with cervicooccipital pain and paresthesia in both arms.

Hepatitis C virus complete life cycle screen for identification of small molecules with pro- or antiviral activity.

Infection with the hepatitis C virus represents a global public health threat given that an estimated 170 million individuals are chronically infected and thus at risk for cirrhosis and hepatocellular carcinoma. A number of direct antiviral molecules are in clinical development. However, side effects, drug resistance and viral genotype-specific differences in efficacy may limit these novel therapeutics.

Negative and positive predictive value of a whole-blood interferon-γ release assay for developing active tuberculosis: an update.

Rationale: only limited data are available on the predictive value of interferon-γ release assays for progression from latent tuberculosis infection to active tuberculosis (TB).

Objectives: to build on our initial study comparing the QuantiFERON-TB Gold in-tube assay (QFT) with the tuberculin skin test (TST) in close contacts of patients with TB and evaluating progression to active TB for up to 4 years.

Methods: a cohort of close contacts of smear-positive index cases established between May 2005 and April 2008 was tested with QFT and TST.

Adaptation of hepatitis C virus to mouse CD81 permits infection of mouse cells in the absence of human entry factors.

Hepatitis C virus (HCV) naturally infects only humans and chimpanzees. The determinants responsible for this narrow species tropism are not well defined. Virus cell entry involves human scavenger receptor class B type I (SR-BI), CD81, claudin-1 and occludin.

Hepatitis C virus enters human peripheral neuroblastoma cells - evidence for extra-hepatic cells sustaining hepatitis C virus penetration.

Patients with chronic hepatitis C virus (HCV) infection show an increased incidence of nervous system disorders such as chronic fatigue syndrome, depression and cognitive dysfunction. It is unclear whether this is because of HCV replication in the brain and in peripheral neuronal cells or to more indirect effects of HCV infection on the central or peripheral nervous system. The aim of this study was to investigate whether cells originating from these tissues are permissive for HCV cell entry, RNA replication and virus assembly.

Know your enemy: translating insights about the molecular biology of hepatitis C virus into novel therapeutic approaches.

Identified in 1989 as the cause of what was then known as hepatitis non-A non-B, the hepatitis C virus (HCV) continues to be a significant global public health threat, given that an estimated 123 million individuals are chronically infected and, thus, at risk for cirrhosis and hepatocellular carcinoma. After 20 years of basic and clinical research into HCV infection, the backbone of therapy has remained interferon, a drug that - in a different formulation - was already being employed before HCV was even identified. Nonetheless, research has overcome many obstacles that stood in the way of studying this pre-eminent human pathogen.

Enhanced cost-benefit analysis of strategies for LTBI screening and INH chemoprevention in Germany.

Objectives: There is only limited economic data in head-to head comparison between a whole blood QuantiFERON TB Gold in tube (QFT) and the tuberculin skin test (TST) when screening and treating for latent tuberculosis infection (LTBI), and no published study to date that takes into account the predictive value of the two tests.

Methods: Health and economic outcomes of isoniazid preventive treatment (IPT) of close contacts were compared in a decision tree model to perform a cost-benefit analysis with respect to isoniazid related hepatotoxicity and early post-exposure TB over a 2-y period, using the QFT or TST alone or QFT as a confirmatory test for TST results.

Results: Cost of screening and treating for using the QFT alone amounted to euro215.

The transcription factors AP-1 and Ets are regulators of C3a receptor expression.

The anaphylatoxin C3a is a proinflammatory mediator generated during complement activation. The tight control of C3a receptor (C3aR) expression is crucial for the regulation of anaphylatoxin-mediated effects. Key factors regulating constitutive expression of the C3aR in the mast cell line HMC-1 and receptor induction by dibutyryl-cAMP in monomyeloblastic U937 cells were determined by functional characterization of the C3aR promoter.