Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function.
Immunity 44(6):1312 (2016)
How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial infections and that these increased acetate concentrations are required for optimal memory CD8(+) T ...
A 'Too Negative' ANA Test Predicts Antibody Deficiency.
Journal of Clinical Immunology 36(4):374 (2016)
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...
N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.
Blood 127(2):216 (2016)
Mutations of the Wiskott-Aldrich syndrome gene (WAS) are responsible for Wiskott-Aldrich syndrome (WAS), a disease characterized by thrombocytopenia, eczema, immunodeficiency, and autoimmunity. Mice with conditional deficiency of Was in B lymphocytes (B/WcKO) have revealed a critical role for WA...
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...
Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency.
Journal of Clinical Investigation 125(11):4135 (2015)
Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not b...
Neutralization of colony-stimulating factor 1 receptor prevents sickness behavior syndrome by reprogramming inflammatory monocytes to produce IL-10.
Brain, Behavior, and Immunity 48:78 (2015)
Sickness behavior syndrome (SBS) as characterized by fatigue and depression impairs quality of life in patients with inflammatory diseases caused by infections and autoimmunity. Systemic engagement of CD40 in mice leads to an inflammatory syndrome with acute hepatitis, lymphadenopathy and develo...
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...
Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency.
Journal of Allergy and Clinical Immunology 135(4):988 (2015)
Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative treatments, such a...
Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels.
PLoS ONE 10(12):e0145635 (2015)
Acute stress drives a 'high-alert' response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans.
3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH...
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...
Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.
Human Vaccines & Immunotherapeutics 11(2):391 (2015)
Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine re...
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...
Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells.
European Journal of Immunology 44(9):2692 (2014)
Patients deficient in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) are predisposed to varied autoimmunity, suggesting it has an important controlling role in participating cells. IL-10-producing regulatory B (Breg) cells are emerging as important mediators of immunosuppress...
Genetic variation in schlafen genes in a patient with a recapitulation of the murine Elektra phenotype.
Journal of Allergy and Clinical Immunology 133(5):1462 (2014)
A common single nucleotide polymorphism impairs B-cell activating factor receptor's multimerization, contributing to common variable immunodeficiency
Journal of Allergy and Clinical Immunology 133(4):1222 (2014)
[Primary and secondary immunodeficiencies].
Therapeutische Umschau 71(1):31 (2014)
Primary Immunodeficiencies (PID) are rare, genetically determined diseases that cause dysfunctional immunity, clinically presenting as susceptibility to infection but also as autoimmunity due to deficient immune tolerance. More than 180 PID have been described to date. To diagnose a PID, seconda...
Usp18 driven enforced viral replication in dendritic cells contributes to break of immunological tolerance in autoimmune diabetes.
PLoS Pathogens 9(10):e1003650 (2013)
Infection with viruses carrying cross-reactive antigens is associated with break of immunological tolerance and induction of autoimmune disease. Dendritic cells play an important role in this process. However, it remains unclear why autoimmune-tolerance is broken during virus infection, but usua...