Tumor-necrosis factor impairs CD4(+) T cell-mediated immunological control in chronic viral infection.
Nature Immunology 17(5):593 (2016)
Persistent viral infections are characterized by the simultaneous presence of chronic inflammation and T cell dysfunction. In prototypic models of chronicity-infection with human immunodeficiency virus (HIV) or lymphocytic choriomeningitis virus (LCMV)-we used transcriptome-based modeling to rev...
Two separate mechanisms of enforced viral replication balance innate and adaptive immune activation.
Journal of Autoimmunity 67:82 (2016)
The induction of innate and adaptive immunity is essential for controlling viral infections. Limited or overwhelming innate immunity can negatively impair the adaptive immune response. Therefore, balancing innate immunity separately from activating the adaptive immune response would result in a ...
Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN-I responses.
European Journal of Immunology 46(2):372 (2016)
Acute or chronic viral infections can lead to generalized immunosuppression. Several mechanisms, such as immunopathology of CD8(+) T cells, inhibitory receptors, or regulatory T (Treg) cells, contribute to immune dysfunction. Moreover, patients with chronic viral infections usually do not respon...
Bile Acid-Induced Suicidal Erythrocyte Death.
Cellular Physiology and Biochemistry 38(4):1500 (2016)
In nucleated cells, bile acids may activate cation channels subsequently leading to entry of Ca2+. In erythrocytes, increase of cytosolic Ca2+ activity triggers eryptosis, the suicidal death of erythrocytes characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryp...
High Frequencies of Anti-Host Reactive CD8+ T Cells Ignore Non-Hematopoietic Antigen after Bone Marrow Transplantation in a Murine Model.
Cellular Physiology and Biochemistry 38(4):1343 (2016)
Graft versus host disease (GvHD) occurs in 20% of cases with patients having an MHC I matched bone marrow transplantation (BMT). Mechanisms causing this disease remain to be studied.
Here we used a CD8+ T cell transgenic mouse line (P14/CD45.1+) and transgenic DEE mice bearing ubiquitously the g...
IL-10 Induces T Cell Exhaustion During Transplantation of Virus Infected Hearts.
Cellular Physiology and Biochemistry 38(3):1171 (2016)
Unexpected transmissions of viral pathogens during solid organ transplantation (SOT) can result in severe, life-threatening diseases in transplant recipients. Immune activation contributes to disease onset. However mechanisms balancing the immune response against transmitted viral infection thro...
Storage of Erythrocytes Induces Suicidal Erythrocyte Death.
Cellular Physiology and Biochemistry 39(2):668 (2016)
Similar to apoptosis of nucleated cells, red blood cells (RBC) can undergo suicidal cell death - called eryptosis. It is characterized by cell shrinkage and phosphatidylserine translocation. Eryptosis is triggered by an increase of intracellular calcium concentration due to activation of nonsele...
Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8(+) T-cell priming and viral control.
Scientific reports 6:19191 (2016)
Clinically used human vaccination aims to induce specific antibodies that can guarantee long-term protection against a pathogen. The reasons that other immune components often fail to induce protective immunity are still debated. Recently we found that enforced viral replication in secondary lym...
Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage.
Immunity 43(5):974 (2015)
Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(-/-...
Deletions in the cytoplasmic domain of iRhom1 and iRhom2 promote shedding of the TNF receptor by the protease ADAM17.
Science Signaling 8(401):ra109 (2015)
The protease ADAM17 (a disintegrin and metalloproteinase 17) catalyzes the shedding of various transmembrane proteins from the surface of cells, including tumor necrosis factor (TNF) and its receptors. Liberation of TNF receptors (TNFRs) from cell surfaces can dampen the cellular response to TNF...
IFN-γ licenses CD11b(+) cells to induce progression of systemic lupus erythematosus.
Journal of Autoimmunity 62:11 (2015)
Autoantibodies are a hallmark of autoimmune diseases, such as rheumatoid arthritis, autoimmune hepatitis, and systemic lupus erythematosus (SLE). High titers of anti-nuclear antibodies are used as surrogate marker for SLE, however their contribution to pathogenesis remains unclear. Using murine ...
Deficiency of the B cell-activating factor receptor results in limited CD169+ macrophage function during viral infection.
Journal of Virology 89(9):4748 (2015)
The B cell-activating factor (BAFF) is critical for B cell development and humoral immunity in mice and humans. While the role of BAFF in B cells has been widely described, its role in innate immunity remains unknown. Using BAFF receptor (BAFFR)-deficient mice, we characterized BAFFR-related inn...
Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase.
PNAS 112(17):5521 (2015)
Urea cycle defects and acute or chronic liver failure are linked to systemic hyperammonemia and often result in cerebral dysfunction and encephalopathy. Although an important role of the liver in ammonia metabolism is widely accepted, the role of ammonia metabolizing pathways in the liver for ma...
T-cell STAT3 is required for the maintenance of humoral immunity to LCMV.
European Journal of Immunology 45(2):418 (2015)
STAT3 is a critical transcription factor activated downstream of cytokine signaling and is integral for the function of multiple immune cell types. Human mutations in STAT3 cause primary immunodeficiency resulting in impaired control of a variety of infections, including reactivation of latent v...
B7-H4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity.
Cancer Immunology Research 3(2):184 (2015)
The B7 family plays a critical role in both positive and negative regulation of immune responses by engaging a variety of receptors on lymphocytes. Importantly, blocking coinhibitory molecules using antibodies specific for CTLA-4 and PD-1 enhances tumor immunity in a subset of patients. Therefor...
NK cells regulating T cell responses: mechanisms and outcome.
Trends in Immunology 36(1):49 (2015)
Natural killer (NK) cells are important innate effectors in immunity. NK cells also have a role in the regulation of the adaptive immune response, and have been shown, in different contexts, to stimulate or inhibit T cell responses. Recent findings have expanded our understanding of the mechanis...
Conjugated bilirubin triggers anemia by inducing erythrocyte death.
Hepatology 61(1):275 (2015)
Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating ...
USP18 Sensitivity of Peptide Transporters PEPT1 and PEPT2.
PLoS ONE 10(6):e0129365 (2015)
USP18 (Ubiquitin-like specific protease 18) is an enzyme cleaving ubiquitin from target proteins. USP18 plays a pivotal role in antiviral and antibacterial immune responses. On the other hand, ubiquitination participates in the regulation of several ion channels and transporters. USP18 sensitivi...
Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection.
Cellular Physiology and Biochemistry 36(6):2379 (2015)
Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-α). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infection...
CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production.
Nature Communications 6:6217 (2015)
B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influ...