Pathogenetic mechanisms and treatment targets in cerebral malaria.

Malaria, the most prevalent mosquito-borne infectious disease worldwide, has accompanied humanity for millennia and remains an important public health issue despite advances in its prevention and treatment. Most infections are asymptomatic, but a small percentage of individuals with a heavy parasite burden develop severe malaria, a group of clinical syndromes attributable to organ dysfunction. Cerebral malaria is an infrequent but life-threatening complication of severe malaria that presents as an acute cerebrovascular encephalopathy characterized by unarousable coma.

OMIP-93: A 41-color high parameter panel to characterize various co-inhibitory molecules and their ligands in the lymphoid and myeloid compartment in mice.

This 41-color panel has been designed to characterize both the lymphoid and the myeloid compartments in mice. The number of immune cells isolated from organs is often low, whilst an increasing number of factors need to be analyzed to gain a deeper understanding of the complexity of an immune response. With a focus on T cells, their activation and differentiation status, as well as their expression of several co-inhibitory and effector molecules, this panel also allows the analysis of ligands to these co-inhibitory molecules on antigen-presenting cells.

Increased Expression of Multiple Co-Inhibitory Molecules on Malaria-Induced CD8 T Cells Are Associated With Increased Function Instead of Exhaustion.

Activated cytotoxic CD8 T cells can selectively kill target cells in an antigen-specific manner. However, their prolonged activation often has detrimental effects on tissue homeostasis and function. Indeed, overwhelming cytotoxic activity of CD8 T cells can drive immunopathology, and therefore, the extent and duration of CD8 T cell effector function needs to be tightly regulated.

T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function in mice.

Overwhelming activation of T cells in acute malaria is associated with severe outcomes. Thus, counter-regulation by anti-inflammatory mechanisms is indispensable for an optimal resolution of disease. Using Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice, we performed a comprehensive analysis of co-inhibitory molecules expressed on CD4 and CD8 T cells using an unbiased cluster analysis approach.

Defective interferon amplification and impaired host responses against influenza virus in obese mice.

Objective: Obesity is a major risk factor that increases morbidity and mortality upon infection. Although type I and type III interferon (IFN)-induced innate immune responses represent the first line of defense against viral infections, their functionality in the context of metabolic disorders remains largely obscure. This study aimed to investigate IFN responses upon respiratory viral infection in obese mice.

Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Malaria.

In malaria, CD8 T cells play a double-edged role. Liver-stage specific CD8 T cells can confer protection, as has been shown in several vaccine studies. Blood-stage specific CD8 T cells, on the other hand, contribute to the development of cerebral malaria in murine models of malaria.

CpG-ODN Facilitates Effective Intratracheal Immunization and Recall of Memory against Neoantigen-Expressing Alveolar Cells.

Intrapulmonary immune reactions are impaired by the tolerogenic environment of the lung. This is manifested by the absence of effective endogenous T cell responses upon neoantigen expression. This tolerance is considered to contribute to lung cancer and inefficient immune therapeutic interventions.

TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall.

Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients.

Diet induced obesity has an influence on intrahepatic T cell responses.

Aim: Obesity is accompanied with systemic inflammation and pre-conditions to severe alterations in liver environment and functions. So far, it remains elusive to which extent obesity modulates immune responses during hepatotropic virus infections as well as in autoimmune hepatitis. In this study we investigated the influence of obesity on the intrahepatic immune response, in particular on the function of CD8 T cells as the crucial players in clearance of virus infected hepatocytes.

The Role of Regulatory CD4 T Cells in Maintaining Tolerance in a Mouse Model of Autoimmune Hepatitis.

Background: The role of regulatory CD4 T cells (Treg) in immune-mediated liver disease is still under debate. It remains disputed whether Treg suppress T cell-mediated hepatitis in vivo and whether hepatic regulatory T cells are functional in patients with autoimmune hepatitis.

Methods: We used TF-OVA mice, which express ovalbumin in hepatocytes, to investigate the impact of Treg in a model of autoimmune hepatitis.

Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.

Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8+ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion.

A BACH2-BCL2L1 fusion gene resulting from a t(6;20)(q15;q11.2) chromosomal translocation in the lymphoma cell line BLUE-1.

Abnormalities of the long arm of chromosome 6 are a common feature in various B-cell malignancies. In most cases, the genes involved have not yet been clearly identified. We have molecularly characterized the recently established Burkitt lymphoma cell line BLUE-1 that carries a t(6;20)(q15;q11.